Human Leukocyte Antigen (HLA) part 71

hla protein 1

 

Therefore, there must be additionally immunological mechanisms that contribute to the protective effect of these HLA alleles in HIV and HCV infection. Several  immunological mechanisms have been suggested contributing to protection by HLA-B-27 including CD8 T cell polyfunctionality (indicated by simultaneous  production of multiple antiviral cytokines) and functional avidity (the sensitivity of CD8 T cells to antigenic stimulation), thymic selection of CD8 T cell precursor (HLA class I alleles that bind few  self-peptides are associated with a greater CD8 T cell precursor   \repertoir and broader cross-reactivity of CD8 T cells, finally leading to superior viral control), specific T cell receptor repertoirs and clonotypes (the selection of T cell receptor clonotypes impact antiviral efficacy and the capacity  to cross-recognize viral variants and in HCV, limited  T cell receptor diversity has been linked to the evolution of viral escape mutations), efficient antigen processing (the amount of peptide produced by the antigen-processing machinery  correlated with magnitude  and requency of HIV and HCV-specific CD8 T cells responses) and evasion from T reg suppression (T regs are thought to suppress HIV and HCV-specific CD8 T cells) and thus contribute to CD8 T cell exhaution snd failure. It has been demonstrate, however, that HIV-specific CD8 T cells restricted by the protective HLA alleles B27 and B57 are not suppressed by T regs

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