Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9802-7. Unique Identifier :
An HLA allele-specific cytotoxic T lymphocyte response is thought to
influence the rate of disease progression in HIV-1-infected individuals.
In a prior study of 139 HIV-1-infected homosexual men, we identified HLA
class I alleles and observed an association of specific alleles with
different relative hazards for progression to AIDS. Seeking an
explanation for this association, we searched HIV-1 protein sequences to
determine the number of peptides matching motifs defined by combinations
of specific amino acids reported to bind 16 class I alleles. Analyzing
complete sequences of 12 clade B HIV isolates, we determined the number
of allele motifs that were conserved occurring in all 12 isolates) and
nonconserved (occurring in only one isolate), as well as the average
number of allele motifs per isolate. We found significant correlations
with an allele's association with disease progression for counts of
conserved motifs in gag (R = 0.73; P = 0.002), pol (R = 0.58, P =
0.024), gp120 (R = 0.78, P = 0.00056), and total viral protein sequences
R = 0.67, P = 0.0058) and also for counts of nonconserved motifs in gag
(R = 0.62, P = 0.013), pol (R = 0.74, P = 0.0017), gp41 (R = 0.52, P =
0.046), and total viral protein (R = 0.71, P = 0.0033). We also found
significant correlations for the average number of motifs per isolate
for gag, pol, gp120, and total viral protein. This study provides a
plausible functional explanation for the observed association of
different HLA alleles with variable rates of disease progression.
*HIV Infections/IMMUNOLOGY *HIV-1/IMMUNOLOGY *HLA Antigens/IMMUNOLOGY
*Viral Proteins/IMMUNOLOGY