HLA-DR is involved in the HIV-1 binding site on cells expressing MHC class II antigens.
The primary interaction of HIV-1 with the target cell involves the viral large envelope protein (gp120) and the cellular CD4 molecule. mAb reacting with portions of CD4 have been shown to block HIV-1 attachment and infection. In one of the early reports describing HIV-1 cell interaction, some mAb reacting with MHC class II Ag were also found to block infection. To investigate further a possible role for MHC class II in HIV-1 binding, a cultured T lymphocyte cell line (H-9) that expresses MHC class II molecules and PHA-stimulated PBL was exposed for various time periods to concentrated viral particles and individual HIV-1 proteins. A decrease in the ability to detect the CD4a epitope and HLA-DR was observed after the cells were exposed to virus for 15, 30, and 60 min whereas HLA-DP and HLA-DQ Ag increased or remained unchanged. After 120 min of virus exposure, the CD4a epitope remained diminished whereas HLA-DR was detected at levels found on cells not exposed to virus. mAb detecting the CD4a epitope and HLA-DR, as well as alloantisera detecting the specific HLA-DR Ag on the target cell, blocked HIV-1 binding. When immunopurified gp120 was added to PHA-stimulated and unstimulated PBL, the CD4a epitope decreased in the same manner as was observed with whole virus preparations. In contrast to exposure to the intact virus, HLA-DR expression appeared to increase. Other viral proteins, p17, p24, and a portion of the small envelope protein, gp41, had no effect on the ability to detect cell surface Ag. Thus, although CD4 is the primary receptor for HIV-1 binding, HLA-DR appears to be involved in the binding site, probably by virtue of its close proximity to the CD4 molecule on the cell surface.
Mann
D L
DL
Section of Biochemical Epidemiology, National Cancer Institute, Bethesda, MD 20892.
Read-Connole
E
E
Arthur
L O
LO
Robey
W G
WG
Wernet
P
P
Schneider
E M
EM
Blattner
W A
WA
Popovic
M
M
D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000032:analysis; D001667:Binding, Competitive; D002460:Cell Line; D006678:HIV / Q000378:metabolism*; D015699:HIV Envelope Protein gp120; D006681:HLA-D Antigens / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007518:Isoantibodies / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins; D015728:Receptors, HIV; D011991:Receptors, Virus / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015699:HIV Envelope Protein gp120; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007518:Isoantibodies; D010835:Phytohemagglutinins; D015728:Receptors, HIV; D011991:Receptors, Virus; D012191:Retroviridae Proteins