Two different groups of
HLA-B specificities were associated with two contrasting outcomes of HIV-1
infection.
HLA-B45, -B49, and -B50 were each found at a moderately increased frequency among individuals responding to HIV-1
infection with a marked circulating and infiltrative CD8 T-cell
lymphocytosis, a slow rate of CD4 T-cell decline, very low frequency of
opportunistic infections, and low viral strain heterogeneity. In contrast, among HIV-infected individuals with more rapid progression to
opportunistic infections,
HLA-B35 was found to be increased in frequency and to act as a dominant marker for this adverse outcome.
HLA-B45, -B49, and -B50 contain identical
peptide-anchoring "B" and "C-terminal" pocket structures, which differ greatly from those present in
HLA-B35, implying that different immunogenic
peptides are likely to be bound by these two groups of alleles. Placing
HLA-B45, -B49, and -B50 into one structurally defined group revealed a much stronger and statistically significant association with the CD8
lymphocytosis syndrome (OR = 5.3, p = 0.0005). The B pocket structure in these alleles contains an easily accessible
lysine residue at position 45, suggesting that the P2 or P3 anchor residue of a bound
peptide is negatively charged. Additionally, by observing the effect on the
ORs of adding structures containing amino acid substitutions in the C-terminal pocket of
HLA-B45, -B49, and -B50, this region was also shown to influence susceptibility to this host response.(ABSTRACT TRUNCATED AT 250 WORDS)