scholarly journals INITIAL CHARACTERIZATION OF MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS IIB EXON 2 IN AN ENDANGERED RATTLESNAKE, THE EASTERN MASSASAUGA (SISTRURUS CATENATUS)

2014 ◽  
pp. 98-104 ◽  
Author(s):  
Collin P. Jaeger ◽  
Richard B. King ◽  
Melvin R. Duvall
Keyword(s):  
Major Histocompatibility Complex ◽  
Positive Selection ◽  
Balancing Selection ◽  
Population Level ◽  
Major Histocompatibility ◽  
Exon 2 ◽  
Conservation Implications ◽  
Histocompatibility Complex ◽  
Sistrurus Catenatus ◽  
Mhc Class Iib

Genes of the major histocompatibility complex (MHC) play an important role in the vertebrate immune system and exhibit remarkably high levels of polymorphism, maintained by strong balancing selection. While the conservation implications of MHC variation have been explored in a variety of vertebrates, non-avian reptiles (most notably snakes) have received less attention. To address this gap and take the first steps toward more extensive population-level analyses, we cloned and sequenced MHC IIB exon 2 in an endangered rattlesnake, the Eastern Massasauga (Sistrurus catenatus). Based on three individuals, we found evidence of at least four putatively functional loci. These sequences exhibited relatively high levels of variation and significantly higher rates of nonsynonymous to synonymous substitutions, especially within the antigen-binding sites, indicating strong positive selection. Phylogenetic analysis revealed a pattern of trans-species polymorphism, also suggesting positive selection. These results contribute to our understanding of MHC variation in non-avian reptiles and form a basis for more studies of MHC variation in snakes of conservation concern.

scholarly journals Impact of Endogenous Intronic Retroviruses on Major Histocompatibility Complex Class II Diversity and Stability

2008 ◽  
Vol 82 (13) ◽  
pp. 6667-6677 ◽  
Author(s):  
Gaby G. M. Doxiadis ◽  
Nanine de Groot ◽  
Ronald E. Bontrop
Keyword(s):  
Major Histocompatibility Complex ◽  
Rhesus Macaques ◽  
Gene Copy Number ◽  
Population Level ◽  
Endogenous Retrovirus ◽  
Copy Number Variations ◽  
Primate Species ◽  
Gene Copy ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

ABSTRACT The major histocompatibility complex (MHC) represents a multigene family that is known to display allelic and gene copy number variations. Primate species such as humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta) show DRB region configuration polymorphism at the population level, meaning that the number and content of DRB loci may vary per haplotype. Introns of primate DRB alleles differ significantly in length due to insertions of transposable elements as long endogenous retrovirus (ERV) and human ERV (HERV) sequences in the DRB2, DRB6, and DRB7 pseudogenes. Although the integration of intronic HERVs resulted sooner or later in the inactivation of the targeted genes, the fixation of these endogenous retroviral segments over long time spans seems to have provided evolutionary advantage. Intronic HERVs may have integrated in a sense or an antisense manner. On the one hand, antisense-oriented retroelements such as HERV-K14I, observed in intron 2 of the DRB7 genes in humans and chimpanzees, seem to promote stability, as configurations/alleles containing these hits have experienced strong conservative selection during primate evolution. On the other hand, the HERVK3I present in intron 1 of all DRB2 and/or DRB6 alleles tested so far integrated in a sense orientation. The data suggest that multigenic regions in particular may benefit from sense introgressions by HERVs, as these elements seem to promote and maintain the generation of diversity, whereas these types of integrations may be lethal in monogenic systems, since they are known to influence transcript regulation negatively.

scholarly journals Highly Restricted T Cell Repertoire Shaped by a Single Major Histocompatibility Complex–Peptide Ligand in the Presence of a Single Rearranged T Cell Receptor β Chain

1998 ◽  
Vol 188 (5) ◽  
pp. 897-907 ◽  
Author(s):  
Yoshinori Fukui ◽  
Osamu Hashimoto ◽  
Ayumi Inayoshi ◽  
Takahiro Gyotoku ◽  
Tetsuro Sano ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Positive Selection ◽  
Peptide Ligand ◽  
T Cell Repertoire ◽  
Major Histocompatibility ◽  
Cell Repertoire ◽  
Histocompatibility Complex ◽  
Self Peptides ◽  
Selection Of

The T cell repertoire is shaped by positive and negative selection of thymocytes through the interaction of α/β-T cell receptors (TCR) with self-peptides bound to self-major histocompatibility complex (MHC) molecules. However, the involvement of specific TCR-peptide contacts in positive selection remains unclear. By fixing TCR-β chains with a single rearranged TCR-β irrelevant to the selecting ligand, we show here that T cells selected to mature on a single MHC–peptide complex express highly restricted TCR-α chains in terms of Vα usage and amino acid residue of their CDR3 loops, whereas such restriction was not observed with those selected by the same MHC with diverse sets of self-peptides including this peptide. Thus, we visualized the TCR structure required to survive positive selection directed by this single ligand. Our findings provide definitive evidence that specific recognition of self-peptides by TCR could be involved in positive selection of thymocytes.

scholarly journals The somatically generated portion of T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Philippa Marrack ◽  
Sai Harsha Krovi ◽  
Daniel Silberman ◽  
Janice White ◽  
Eleanor Kushnir ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Structural Basis ◽  
Major Histocompatibility ◽  
Cell Receptors ◽  
Histocompatibility Complex

Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.

scholarly journals Turkey humoral and cell-mediated immune responses to a Newcastle viscerotropic vaccine and its association with major histocompatibility complex.

2019 ◽  
Vol 22 (1) ◽  
pp. 26-40
Author(s):  
H. Al-Karagoly ◽  
G. Nikbakht ◽  
M. Hassanzadeh ◽  
T. Tolouei
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune Responses ◽  
Mhc Class Ii ◽  
Cellular Response ◽  
Class Ii ◽  
Secretory Iga ◽  
Enzyme Linked Immunosorbent Assay ◽  
Major Histocompatibility ◽  
Exon 2 ◽  
Histocompatibility Complex

Immune responses to vaccines are mainly influenced by the nature of vaccines and host variation in response to vaccination. In this study we aimed to investigate turkey humoral and cell-mediated immune responses to a Newcastle viscerotropic vaccine and its association with major histocompatibility complex (MHC). Turkeys were vaccinated with Villegas–Glisson/University of Georgia (VG/GA) attenuated vaccine against Newcastle disease. The stimulation index of lymphocyte proliferation and antigen-specific local secretory IgA responses in bile, duodenum, ileum, as well as serum IgY and IgA responses were analysed by enzyme-linked immunosorbent assay. The turkey MHC class II B locus was selected as candidate gene for detection of associations with cellular and humoral immune responses. Significant differences were observed between both cellular and humoral responses of vaccinated and unvaccinated groups. A significant positive correlation was also found between ND specific IgY and ND specific IgA titres in serum, intestine (duodenum and ileum) and trachea. Moreover, the correlation between specific IgA titres in ileum and specific bile, duodenum and trachea was positively significant. High resolution melting analysis (HRM) was used to genotype MHC class II B exon 2. Eight melting profiles (A-G) were identified, among which, profile G showed a significant association with cellular response. The profile B revealed significant association with total IgA titres in serum and ileum. These findings help our understanding of the association of turkey MHC types with immune responses. Further correlation analysis between serum and mucosal antibody titres demonstrated that the levels of IgY and IgA in serum can give an impression about the levels of secretory IgA and situation of mucosal immunity. Based on the significant effects, ND specific IgY in serum appears to be a promising indirect marker for specific IgA in serum and trachea.

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