HLA tapasin independence: broader peptide repertoire and HIV control

Abstract

Human leukocyte antigen (HLA) class I allotypes vary in thei ability to present peptides in the absence of tapasin, an essentia component of the peptide loading complex. We quantified tapasi dependence of all allotypes that are common in European an African Americans (n = 97), which revealed a broad continuum o values. Ex vivo examination of cytotoxic T cell responses to th entire HIV-1 proteome from infected subjects indicates tha tapasin-dependent allotypes present a more limited set of distinc peptides than do tapasin-independent allotypes, data supporte by computational predictions. This suggests that variation in tapa sin dependence may impact the strength of the immune response by altering peptide repertoire size. In support of this model, w observed that individuals carrying HLA class I genotypes charac terized by greater tapasin independence progress more slowly t AIDS and maintain lower viral loads, presumably due to increase breadth of peptide presentation. Thus, tapasin dependence level like HLA zygosity, may serve as a means to restrict or expan breadth of the HLA-I peptide repertoire across humans, ultimatel influencing immune responses to pathogens and vaccines.