Certain HLA-DR5 and -DR6 major histocompatibility complex class II alleles are associated with a CD8 lymphocytic host response to human immunodeficiency virus type 1 characterized by low lymphocyte viral strain heterogeneity and slow disease progression.
Either of two structurally related major histocompatibility complex class II alleles, DRB1*1102, which encodes a DR5 specificity, or DRB1*1301, which encodes a DR6 specificity, was found in 67% of individuals responding to human immunodeficiency virus type 1 (HIV-1) infection with a syndrome characterized by persistent circulating and diffusely infiltrative CD8 lymphocytosis (DILS), slow progression to opportunistic infections, and delayed CD4 T-cell depletion. These alleles were present in only 28% of ethnically matched HIV-positive controls (P = 0.001). The frequency of DRB1*1301 was increased in both Blacks and Caucasians with this syndrome, while that of DRBI*1102 was increased only in Blacks, where 80% had either of these alleles. To investigate whether the host response associated with these alleles influences the evolutionary divergence of the HIV-1 genome, sequencing of the envelope V3 loop was performed. This revealed a significantly diminished lymphocyte viral heterogeneity compared with random HIV+ controls matched for CD4 T-cell levels. These results suggest that the immunogenetics of the host influence the nature of the immune response to HIV-1, which may lead to constrained evolution of HIV-1 gene products. Of possible relevance, the alpha-helical third diversity region common to both the DRB1*1102 and DRB1*1301 allelic products was noted to have homology with the C-terminal region of the HIV-1 envelope V3 loop at six of nine consecutive residues. This suggests the possibility that these alleles may bias the anti-HIV T-cell receptor repertoire through a mimicry mechanism.
Itescu
S
S
Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Rose
S
S
Dwyer
E
E
Winchester
R
R
D000483:Alleles; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005006:Ethnicity; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics*; D015805:HLA-DR5 Antigen / Q000276:immunology*; D015808:HLA-DR6 Antigen / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D008218:Lymphocytosis / Q000276:immunology*; D008969:Molecular Sequence Data
D015699:HIV Envelope Protein gp120; D006684:HLA-DR Antigens; D015805:HLA-DR5 Antigen; D015808:HLA-DR6 Antigen; D059811:HLA-DRB1 Chains