The impact of HLA-B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV

Abstract

The factors controlling epitope selection in the T cell response to persistent viruses are not fully understood, and we have examined this issue in the context of four HLA-B*35-binding peptides from the pp65 antigen of human cytomegalovirus, two of which are previously undescribed. Striking differences in the hierarchy of immunodominance between these four epitopes were observed in healthy virus carriers expressing HLA-B*3501 versus B*3508, two HLA-B allotypes that differ by a single amino acid at position 156 (HLA-B*3501, (156)Leucine; HLA-B*3508, (156)Arginine) that projects from the alpha2 helix into the centre of the peptide-binding groove. While HLA-B*3501(+) individuals responded most ..