Curr. Protoc. Immunol. 91:14.16.1-14.16.15. © 2010 by John Wiley & Sons, Inc. “
“Inflammatory biomarkers are associated with preeclampsia (PE) and poor fetal growth; however, genetic epidemiologic studies have been limited by reduced gene coverage and the exclusion of African American mothers. Cases and controls (N = 1646) from a pregnancy cohort were genotyped for 503 tagSNPs in 40 genes related to inflammation. Gene-set analyses were stratified by race and were followed by a single SNP analysis within significant gene sets. Gene-level associations were found for

IL6 and KLRD1 for term small for gestational age (SGA) among African Americans. LTA/TNF and TBX21 were associated with PE among European Americans. The strongest association was for PE among European Americans for an upstream regulator of TNF with RR = 1.8 (95% Angiogenesis inhibitor CI 1.1–2.7). Although previous studies have suggested null associations, increased tagging and stratification

by genetic ancestry suggests important associations between IL6 and term SGA for African Americans, and a TNF regulator and PE among European Americans (N = 149). “
“IL-2 Selleck Cisplatin was discovered as a T-cell growth factor that promoted T-cell-dependent immune responses; however, more recent studies suggest that the essential role of IL-2 is to maintain functional Treg and thus control immune responses. These results are leading to new ideas about the potential of IL-2 as a therapeutic strategy in autoimmune diseases. In this issue of the European

Journal of Immunology, a study further examines the role of IL-2 in immune regulation and shows for the first time that IL-2 complexes can ameliorate autoantibody-mediated autoimmunity. This commentary examines the current findings in relation to what we already know about IL-2 complexes. IL-2 was initially discovered due to its activity in vitro as a growth factor for T cells 1, and was first used as a therapeutic approach in humans to boost immune responses in patients with disseminated cancer 2 and advanced HIV disease PIK3C2G 3. These therapeutic attempts, however, have had limited success. The generation of mice deficient in IL-2 or components of the IL-2 receptor 4–6 challenged the notion that promoting T-cell expansion and differentiation into effector cells is the main function of IL-2 in the immune system. The observation that mice lacking IL-2 or the IL-2R developed lymphoproliferation and autoimmune disease suggested a growth-limiting, rather than a growth-inducing, function of IL-2. Initial attempts to understand the mechanism underlying the inhibitory role of IL-2 in T-cell responses led to the observation that IL-2 sensitized activated T cells for activation-induced cell death 7. These experiments were mostly done with in vitro T-cell cultures and evidence that IL-2-dependent activation-induced cell death indeed suppresses in vivo T-cell responses remains limited.

The aGVHD is produced by an allogenic immune response in a predominant milieu of Th1-type cytokines [37]. These findings U0126 mouse suggest that CD30 expression is not only dependent on cytokines produced by Th2-type cells. Accordingly, significant serum CD30s levels have been associated with another immune disease mediated by Th1-type response as in rheumatoid arthritis

[38]. Equally, we have found in the CD30 correlation study carried out in patients with SLE, a positive correlation between IL-4 (Th2), IFNγ (Th1) and immunosuppressive cytokines (IL-10 and TGFβ). Results support the presence of an imbalance in both the Th2-/Th1- and Treg-type cytokines. CD30 has pleiotropic biological functions, and it is capable of promoting cell proliferation and survival as well as inducing antiproliferative responses

and cell death [39, 40]. The CD30/CD30L signalling pathway is barely known and could be a potential therapeutic target in autoimmune diseases such as SLE [12, 13, 25]. Indeed, at present, there are developed preclinical and clinical studies with monoclonal antibodies targeting the CD30/CD30L signalling pathway. This work was supported by the grant PI-2009/25 from CH5424802 purchase the Castilla-La-Mancha Foundation for Health Research (Fundación para la Investigación Sanitaria en Castilla La Mancha (FISCAM)). “
“The immune system of pregnant women is tightly controlled to defend against microbial infections and at the same time, to accept an embryo or the fetus, which are expressing semi-allogenic paternal antigens. Furthermore, inflammation-like processes are crucial for tissue growth, remodeling, and differentiation of the decidua during pregnancy. Dysregulation of elaborate immune control may lead reproductive failure, such as implantation failure, recurrent

pregnancy loss (RPL), preterm birth, intrauterine fetal growth restriction, and preeclampsia. Until recent years, a balance between Th1 and Th2 cells was believed to be the key immune regulatory mechanism of T-cell immunology filipin especially during pregnancy. Since the identification of regulatory T cells was made, the mechanism of immune regulation has become a major issue in immunologic research. Also, the recent identification of Th17 cells has drawn our attention to a new immune effector. The balance between Th17 and regulatory T cells may explain more about the pathophysiology of reproductive failure. This review will discuss relevant human literature on regulatory T and Th17 cells in normal reproductive physiology and in women with RPL and infertility. During pregnancy, the immune system of the mother is tightly controlled to defend against microbial infections and to accept an embryo and a fetus, which are expressing semi-allogenic paternal antigens. Furthermore, immune-mediated processes such as tissue growth, remodeling, and differentiation are crucial to maintain pregnancy.

Conclusion: The fructuation of CH50 after the transition to on-line HDF was

correlated with nutrition status such as TP, Alb, UA, K or cholesterol, and might be one of the early indicators for permanence of on-line HDF. KIMURA KEIKO1, KASUGA HIROTAKE1, TAKAHASHI RYO1, MATSUBARA CHIEKO1, KAWASHIMA KIYOHITO1, KAWAHARA HIROHISA1, this website MIZUNO MASASHI2, SUZUKI YASUHIRO2, MARUYAMA SHOUICHI2, ITO YASUHIKO2, MATSUO SEIICHI2 1Nagoya Kyoritu Hospital; 2Nephrology, Nagoya University Nagoya University Introduction: Ankle brachial index (ABI) has been widely recognized as a marker of systemic atherosclerosis in various population including hemodialysis (HD) patients. Protein-energy wasting (PEW), currently considered to be due to inflammatory process rather than poor nutritional intake, is highly prevalent in HD patients, and is also associated with increasing risk of mortality. We investigated the association of ABI and PEW with mortality in HD patients. Methods: A total of 1036 HD patients were divided into three groups according to ABI Sorafenib levels; normal group: 0.9–1.4 (n = 682), high group: >1.4 (n = 150) and low group: <0.9 (n = 204) and were also divided into tertiles according to geriatric nutritional risk index (GNRI) levels as a simplified marker of PEW state; tertile 1 (T1): <90.8, T2: 90.8–97.3 and T3: >97.3 (Table 2). GNRI was calculated as follows; GNRI = (14.89 × albumin) + [41.7 × (body

weight Thiamine-diphosphate kinase / body weight at BMI of 22)]. They were followed up for 8 years. Results: Declined GNRI levels were independently associated with abnormal ABI (<0.9 or >1.4) (odds ratio 0.97, 95%CI 0.96–0.99, p = 0.0009). By Kaplan-Meier analysis, 8-year event-free survival rates from mortality were 62.8%, 46.2% and 27.3% among normal,

high and low ABI group (p < 0.0001), and were 34.3%, 59.7% and 68.0% among T1, T2 and T3 of GNRI, respectively (p < 0.0001). After adjusting for other confounders, both ABI and GNRI were independent predictors for mortality. In the combined setting of ABI and GNRI, the risk of mortality was 4.26-fold (95%CI 2.63–6.90) higher in the low ABI group with T1 of GNRI and 3.69-fold (95%CI 2.30–5.91) higher in the high ABI group with T1 of GNRI compared to the normal ABI group with T3 of GNRI, respectively Similar results were also obtained from cardiovascular mortality. Conclusion: Abnormal ABI and lower GNRI, might reflect PEW state, were closely linked, and were additively associated with increasing risk of mortality in HD patients. ZHAO LIJUN1, HUANG SONGMIN1, LIANG TING2, TANG HONG2 1Department of Nephrology, West China Hospital of Sichuan University; 2Department of Cardiology, West China Hospital of Sichuan University Introduction: While chronic dialysis therapy has been exhibited a high prevalence of pulmonary hypertension, occurrence of right heart failure during dialysis treatment is associated with high mortality in patients with pulmonary hypertension.

No statistical difference between the levels of IFN-γ in CFP-10 test was observed between the LTBI and NC groups and TB (latent infection + disease) and NC groups (data not shown). Tavares et al. [26] and Hill et al. [47] obtained similar results, where the response of IFN-γ levels against CFP-10 was lower than that found against ESAT-6.

When the ROC curve analysis was performed, no statistically significant difference between the groups was observed, even between the TB disease and NC groups (P = 0.076), indicating that the antigen CFP-10 is not a good diagnostic tool for childhood TB. Arend et al. [40] also observed Dorsomorphin that most TB suspects responded to the antigen ESAT-6, but not to CFP-10. One possible reason for this is that the presence of HLA-DR15, which is the major DR2 subtype, is strongly associated with high responses of CD4+ T cells to the CFP-10 antigen [39], indicating a greater susceptibility

to infection by M. tuberculosis in populations where this gene is expressed [48]. The absence of expression of this gene in a specific population causes a reduced or even absent response to CFP-10, as different populations differ in antigen processing and recognition of antigenic epitopes by T cells, thereby explaining the genetic polymorphism found among populations [47] and the differences between the immune responses observed against the same antigen. Other studies corroborate the idea that the host’s immunogenetic Romidepsin background is a decisive factor in the immunological response of specific T lymphocytes to CFP-10 antigen stimuli when it is presented by macrophages or other antigen-presenting cells [49]. It is possible that the epitope recognized by the induced T cells is not presented or presented inefficiently by M. tuberculosis-infected cells. This would explain why the DNA vaccine using CFP-10 antigens protect some species of mice from M. tuberculosis, as was observed by Wu et al. [50], although the same finding was not produced by Mollenkopf et al.

[49]. Mustafa et al. [51] argue that the variability of sensitivity and specificity found in tests using CFP-10 as the antigen is determined by factors that are intrinsic to the bacterium, such as the abundance of the protein, Protirelin its subcellular location, post-translational modification, participation in macromolecular complexes and in vivo regulation. They also cite factors relating to the antigen-presenting cell, including location with respect to the phagosome, proteolytic sensitivity and the presence of motifs suitable for interaction with TAP transporters and different MHC alleles. De Meher et al. [52] found a weak ligation among CFP-10 antigens among bilayers presenting cells, suggesting that this antigen might only remain loosely attached, which corroborates the findings of de Jonge et al. [53], in which ESAT-6 shows greater T-cell activation compared to the ESAT-6-CFP-10 complex.

Yet, this BMN 673 price has been documented in rare cases [14]. The only instance in which priming of these responses has been shown to occur in a consistent manner is in HLA-A2+ individuals with advanced metastatic melanoma [5, 12].

On the other hand, a peculiar structural feature also contributes to the abundance of Melan-A tetramer+ CD8+ T cells independently of the expression of the HLA-A2+ presenting allele. The TRAV-12-2 (formerly known as Vα2.1) TCR segment is over-represented in CD8+ T cells of this specificity so that over 90% of specific T cells express this particular segment, compared to an overall frequency in bulk CD8+ T cells of 6–8% [15, 23, 24]. At this juncture, there were still major questions left open. What is the exact reason for the preferential selection of the TRAV12-2 segment-containing TCR alpha chains? What supports a robust thymic output of Melan-A/MART-1-specific TCRs in the face of detectable expression of the Melan-A gene in mTECs [25]. Should thymic expression of Melan-A/MART-1 not lead to the negative

selection of high-affinity, specific CD8+ T cells? It was assumed that this was probably Dabrafenib nmr the case and that the repertoire was devoid of the latter cells. The measurement of specific TCR binding parameters, however, suggested the existence of a large range of avidities [26] (and our unpublished data). In this issue, Sheena Pinto et al. [27] elegantly provide definitive answers for these two questions. First, the authors introduced PAK6 a single codon mutation, changing glutamine at position 31 of the CDR1 domain encoded in the TRAV12-2 gene segment, and could practically abrogate tetramer binding by T cells made to express the mutant TCR. This experiment nicely confirms and extends the structural data provided earlier by another group on the three dimensional structure of a HLA-A2/Melan-A/TCR pentamolecular complex [28]. Thus, this CDR1α, encoded in the germ line, exhibits selective affinity for the complex HLA-A2/ELAGIGILTV, whereby multiple electrostatic interactions formed between

Gln on the CDR1 domain and several amino acid residues, including Glu at P1, on the antigenic peptide provide most of the binding energy. This is also the likely explanation for the high frequency of “allorestricted” tetramer binding CD8+ T cells found in most HLA-A2– individuals. Second, the apparent paradox of productive thymic output of self/Melan-A-specific TCRs with a wide range of avidities despite the expression of Melan-A transcripts in the mTECs is now resolved in an unexpected and interesting fashion. Pinto et al. report that the predominant Melan-A transcript that can be found in mTECs is a truncated one, the product of misinitiation of transcription [27]. Consequently, the protein product lacks the immunodominant epitope as the first three exons are not transcribed. Thus, the epitope spanning residues 26–35 is not expressed in mTECs and central tolerance is simply not operating in this particular instance (Fig. 1).

The salvage of hardware and reconstruction BMN673 of soft tissue defect remain challenging. In this report, we presented our experience on the use of the distally based saphenous neurocutaneous perforator flap combined with vacuum-assisted closure (VAC) therapy for the coverage of the soft tissue defect and the exposed hardware in the lower extremity with fracture. Between January 2008 and July 2010, seven patients underwent the VAC therapy followed by transferring a reversed saphenous neurocutaneous perforator flap for reconstruction of the wound with exposed hardware around the distal tibia. The sizes of the flaps ranged

from 6 × 3 cm to 15 × 6 cm. Six flaps survived completely. Partial necrosis occurred in one patient. There were no other complications of repair and donor sites. Bone healing was achieved in all patients. In conclusion, the reversed saphenous neurocutaneous perfortor flaps combined with the VAC therapy might be one of the options to hypoxia-inducible factor cancer cover the complex wound with exposed hardware in the lower extremities. © 2013 Wiley Periodicals, Inc. Microsurgery 33:625–630, 2013. “
“Postoperative flap

monitoring is a key component for successful free tissue transfer. Tissue oxygen saturation measurement (TOx) with near-infrared spectrophotometry (NIRS) is a method used for this purpose. The aim of this study was to identify external variables that can affect TOx. Patients who had breast reconstruction with free flaps were monitored cAMP prospectively and intra-operative details were recorded. Flap TOx was recorded with NIRS pre-extubation, postextubation, and then every four hours for 36 hours. At each of these time points, blood oxygen saturation (SO2), amount of supplemental oxygen, and blood pressure were recorded. Thirty flaps were monitored. Initially, a significant trend over time was detected such that for every increase of 24 hours, TOx decreased on average by 2.1% (P = 0.025). However, when accounting for SO2 levels, this decrease was no longer significant

(P = 0.19). An increase by 1% in SO2 produced an increase in TOx reading of 0.36 (P = 0.007). The amount of supplemental O2, systolic blood pressure, and diastolic blood pressure did not have a significant impact on TOx (P > 0.05). The TOx values were highest in the free TRAM flaps and were lower in decreasing order in the muscle-sparing TRAM, DIEP, and SIEA flaps (P > 0.05). The TOx values did not significantly correlate with vessel size, perforator number, or perforator row. Postoperative flap TOx was found to correlate with SO2 and was not significantly dependent on blood pressure, supplemental O2, or surgical variables. Careful interpretation of oximetry values is essential in decision making during postoperative flap monitoring. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014.

In human desensitizations High Content Screening the level of IgE sensitization varies and is unknown for each patient and the target dose used for desensitization is empirical, which impacts its safety 4, 5, 8. The mechanism of desensitization is not fully understood and we have observed that low antigen doses induce small amounts of extracellular calcium

flux, indicating the mobilization of endoplasmic reticulum stores, enabling functional CRAC channels to open 17. The sequential delivery of low antigen doses during desensitization may provide continued low levels of calcium entry with conformational changes of CRAC and other calcium-related channels locking further calcium entry and blocking signal transduction. Because calcium entry is clearly specifically impaired in our model, since a second non-desensitizing antigen allowed restoration of calcium flux, membrane compartmentalization may be required to exclude signal transduction molecules Roxadustat molecular weight around desensitized receptors. We observed

that in desensitized cells, phosphorylation of STAT6 and p38 MAP kinase was impaired and consequently TNF-α and IL-6 production was diminished. Since earlier studies indicated that STAT6-null BMMCs could not be desensitized 16, it is possible that STAT6 activity is required for desensitization, via a pathway different from the one leading to the acute and late activating responses. Our system is limited by the fact that BMMCs are cultured in IL-3, which may affect cytokine production 24. Nonetheless, this may have an important correlate in human desensitizations since our group has not observed delayed reactions in desensitized patients, confirming that the inhibition of mast cell activation Methisazone during desensitization prevented later hypersensitivity reactions 4, 5. Maintenance of hypo-responsiveness in desensitized cells was not sustained by the presence of an excess of soluble antigen since washed cells remained desensitized. It is possible that bound antigen is equilibrated in desensitized

cells. Earlier studies 12, 13 suggested that the hypo-responsiveness induced by desensitization was due to internalization of antigen/IgE/FcεRI complexes and that the lack of available IgE renders the cells refractory to further stimulation. In contrast, we show here that, unlike activation, internalization of IgE and FcεRI is impaired during specific desensitization (Fig. 4A) and that desensitized cells can be triggered by anti-IgE, since unbound IgE remains accessible and is available for crosslinking (Fig. 4B). Saturating doses of IgE in a co-culture system and the use of higher antigen doses 12 may promote internalization while low doses may redistribute antigen-bound receptor at the membrane level. Moreover, others have shown that low doses of antigen induce antigen-crosslinked receptors to remain mobile on the cell surface 25. In addition, microscopy studies gave us the opportunity to directly look into antigen localization after desensitization.

[13, 14] Similar studies in patients with haematological malignancies and HSCT[15-18] or solid organ transplantation[19, 20] with invasive aspergillosis have demonstrated several prognostic risk factors of mortality, which may assist in the development of treatment intensity algorithms and clinical trials. In our univariate analysis, 12 such variables were found to be significantly different between 4-week survivors and non-survivors; male sex, total bilirubin, thrombocytopenia, LDH, creatinine clearance, acidosis, GvHD, active malignancy,

severe neutropenia, lymphocytopenia, monocytopenia and voriconazole breakthrough infection. Nevertheless, multivariate analysis accounting for severity of underlying disease revealed only baseline severe lymphocytopenia and a high LDH serum level (>655 mg dl−1) LGK-974 research buy as independent predictors of early death. INK 128 molecular weight Consequently, we identified two different prognostic groups using these variables: patients with a 28-day crude mortality rate of <15% (score ≤22) and

patients with a mortality rate of 75% (score >22). The outcome of mucormycosis depends on several factors, including the site of infection, the immune status of the host and the use of surgery or other adjunctive treatments.[21, 22] Chamilos et al. [7] reported that the initiation of polyene therapy within 5 days after diagnosis of mucormycosis was associated with improvement in survival, compared with initiation of polyene therapy at ≥6 days after diagnosis (83% vs. 49% survival). In the same study,

active malignancy (P = 0.003) and monocytopenia (P = 0.01) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy (P = 0.01) and neutrophil recovery (P = 0.009) were predictive of a favourable outcome.[7] However, this analysis included patients prior to 2000 when diagnosis and treatment outcomes were considerably worse than the Obatoclax Mesylate (GX15-070) current era. Likewise, previous investigators have emphasised the important role of early neutrophil recovery and treatment with high-dose amphotericin B.[23-25] Of interest, a recent prospective study on 20 patients with mucormycosis (with pulmonary and non-pulmonary sites of infection) showed that active malignancy (P = 0.03), neutropenia (P = 0.03) and iron overload (P = 0.03) were significantly associated with 90-day mortality in univariate analysis, whereas no association was found with amphotericin B dose or the use of other antifungal therapy (i.e. echinocandin and posaconazole).[8] Nevertheless, in the current study, only lymphocytopenia and high LDH levels, which probably reflects activity of the underlying malignant disease, were significant risk factors for poor outcome when analysis was adjusted for underlying severity of illness (APACHE II).

Demyelination was still obvious in LFA-1−/− mice (4.57±1.73%) but almost completely absent in LFA-1+/+ mice (0.12±0.33%). To further analyze the cellular composition of the infiltrates, we prepared single-cell suspensions from selleck products spinal cords by mechanical disruption and enzymatic

digestion with collagenase. As expected, the total number of cells obtained from spinal cords of LFA-1−/− mice was much higher compared with LFA-1+/+ mice (Fig. 3A). To get more information about the composition of the infiltrates, we used cell subset-specific markers in flow cytometry. Next to microglia, CD4+ T cells represented the major leukocytic population in the spinal cord. Additionally, we found B cells, very few CD8+ T cells, NK cells, NK T cells, γδ T cells, conventional dendritic cells, and plasmacytoid dendritic cells. All these latter populations did not differ Decitabine mouse significantly between LFA-1−/− and LFA-1+/+ mice. Autoantigen-specific CD4+ T cells are known to be the major pathogenic factor in EAE 8. To get information not only about total but MOG-specific CD4+ T cells, we used a recently established system to detect antigen-specific

T cells with high sensitivity 9. The method is based on a short-term in vitro restimulation with the cognate antigen and subsequent staining for CD40L (CD154). This assay revealed that up to 50% of the infiltrating CD4+ T cells were specific for the autoantigen. Importantly, the frequency of MOG-specific CD4+ T cells was approximately two-fold higher in LFA-1−/− compared with LFA-1+/+ mice (Fig. 3A). In combination ADAMTS5 with the higher absolute cell numbers, this results in an about five-fold increased number of autoreactive T cells in the spinal cord of LFA-1 KO mice, which can easily explain the more aggravated disease. The frequency of autoreactive T cells directly correlated with disease severity (r=0.82, p=0.0003 for the experiment shown in Fig. 3). It is important to note that the higher cell number cannot be explained by different kinetics of lymphocyte infiltration because

comparable results were obtained regardless whether both groups were analyzed at the same time point (which was not necessarily the peak of clinical signs for both groups) or the peak of the clinical score for individual animals. As LFA-1 was shown to be involved in lymphocyte migration 10, 11, it is tempting to speculate that the higher number of MOG-specific T cells in the spinal cord of LFA-1 KO mice is the result of an enhanced recruitment to the site of inflammation. However, when we used the same strategy to identify MOG-specific T cells in secondary lymphoid organs, it turned out that the difference in antigen-specific T cells was already established in the spleen and the draining lymph nodes (Fig. 3B). Therefore, LFA-1 seems to control the generation and not the distribution of antigen-specific T cells. Pro-inflammatory cytokines, namely IL-17 and IFN-γ, are well recognized as major pathogenic factors in EAE 8.

4, Supporting Information Fig. 4 and Table 1). In the TCRGV2-TCRGJ2-2 cDNA clones nine tandem mutations are also present. Since the mRNA sample was prepared from the spleen tissue of a single animal, the sequence diversity observed cannot be explained by allelic variations, nor can it be due to PCR errors because a high-fidelity polymerase was used. The rare occurrence of changes in C region sequences, the absence of changes in nine of the V domain sequences, and the presence see more of the

same mutation in different clones confirms the high fidelity of the polymerase used. The changes observed consisted of 213 nucleotides substitutions, with an overall frequency of 0.008 per base pair (Table 1), much higher than that of a nonrelevant gene (EEF1A1) [14]. The average mutation rate does not depend on the number of PCR cycles,

given that 19 of 22 TCRGV1-TCRGJ1-1 cDNA clones were obtained by half the number of PCR cycles with respect to the TCRGV2-TCRGJ2-2 clones. To exclude the presence of large germline TCRGV gene subfamilies, Southern blotting and quantitative real-time PCR were performed (Supporting Information Fig. 5A–C). Both assays confirmed the TCRG locus arrangement and the sequencing data, i.e. the TCRGV1 and TCRGV2 subgroup is represented by a single gene per haploid CH5424802 genome. Genealogy clonal trees of mutants TCRGV2 sequences within a single rearrangement (Fig. 4) are presented in Fig. 5. Thus, these data demonstrate that somatic mutation occurs in both the dromedary TCRGV and TCRDV region [14], as well as in the sandbar shark TCRGV [13]. The TCR γ chain mutations do not show any bias for transition/transversion changes (Supporting Information Table 2A and B). The target bases are slightly biased toward G and C bases and (A/G/T)G(C/T)(A/T) motif (or DGYW) or its reverse complement (A/T)(A/G)C(C/T/A) (or WRCH), as has been PJ34 HCl shown for IG genes [11, 23]. We were not able to observe a targeting of mutations to

CDR rather than to framework region (FR) (Table 2). The IG mutations from mammals are conventionally evaluated by comparing replacement and synonymous substitutions (R/S ratios) in CDR and FR regions. The ratio in dromedary TCR V domains is higher for CDR than for FR (Table 2), suggesting either selection toward amino acid (AA) changes in CDR or against AA changes in FR. Structural models of the V domains obtained by joining AA sequences of V and J germline TCRGV1-J1-1 (VG1), TCRGV2-J2-2 (VG2), and TCRDV4-TCRDJ4 (VD4) [14] and of VG1/VD4, VG2/VD4 Fv were computed adopting a comparative modeling procedure. Templates were the counterpart γδ subunits of the human γδ T-cell receptor (PDB code: 3 omz) [24, 25]. VG1 and VG2 share a sequence identity of only 29%. However, their 3D structure is highly similar (with a root mean square deviation (RMSD) of 0.69 Å, calculated on the backbone) and they similarly interact with the computed VD4.