![]() ![]() KK10 requires a series of complex mutations, both internal and external to the epitope, to enable the emergence of a successfully mutated epitope that evades immune recognition with eventual onset of AIDS ( 2). ![]() The preference for individual MHC class I alleles might reflect their ability to present conserved viral epitopes to CD8 + T cells the conservation of a single immunodominant epitope, namely the gag-derived KRWIILGLNK (KK10) peptide, appears to account for the association of B*27 with prolonged AIDS-free survival in infection. The heterozygous advantage at the MHC class I locus probably reflects the availability of distinct MHC class I molecules to present diverse epitopes to T lymphocytes, resulting in broader immune responses, and delaying the incidence of viral immune evasion. The influence of the MHC class I loci on clinical outcome warrants further investigation to further our understanding of disease pathogenesis and to direct the generation of effective vaccines. Collectively, our findings highlight unusual features of the B*5701/B*5703-KF11-specific immune responses which could influence disease progression and that might be important to consider when designing future vaccine regimens. We now report striking features of TCR conservation both in terms of TCR Vα and Vβ chain usage, and throughout the hypervariable region. Recently, we also elucidated the highly distinct structure of KF11 in complex with B*5703, and have now characterized the CD8 + T cell repertoire recognizing this epitope. By combining structural and cellular studies, we now demonstrate that the KF11 and epitopes induce distinct functional responses in and KF11-specific T cells, respectively, despite minimal structural differences between the individual B*57-peptide complexes. Previously, we observed that the KF11 clade variants KGFNPEVIPMF and KAFNPEIIMPF, sharing a position 4 mutation, are differentially recognized by KF11-specific T cells. In this study, we evaluate the B*57-restricted p24 KAFSPEVIPMF (KF11) immune response which is immunodominant during chronic infection. HLA-B*57 is associated with slower disease progression to AIDS, and CD8 + T cell responses to B*57-restricted epitopes are thought to contribute to this protective effect.
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