Common sequence in HIV 1 GP41 and HLA class II beta chains can generate crossreactive autoantibodies with immunosuppressive potential early in the course of HIV 1 infection.
We have previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV 1 gp41 (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25). Murine monoclonal antibodies raised against synthetic peptides from these homologous regions bound not only to the isolated peptides, but also to "native" HLA class II molecules on cells. Screening of sera from HIV 1 infected individuals revealed high frequency of sera (35%) containing anti-class II crossreactive antibodies (CRAb), not only in AIDS patients, but also in early, asymptomatic patients. The CRAb containing sera caused potent inhibition of normal CD4-bearing cells' proliferative responses to tetanus toxoid in vitro. They could also kill class II bearing cells by ADCC. The possible contribution of these antibodies to the establishment of immunodeficiency state in HIV 1 infected individuals and/or to disease progression, was examined in two clinical studies: I. Asymptomatic patients were tested in parallel for their PBL responses to flu/tetanus, HLA alloantigens, and PHA (proliferation and IL2 production), and for the presence of anti-class II CRAb. About 50% of these patients showed a selective loss of their in vitro responses to recall antigens (flu/tetanus), which depend on CD4+ cells, while still responding to PHA and ALLO. Interestingly, positive correlation was found (P less than 0.001) between patients' lack of responsiveness to flu/tetanus and the presence in their sera of anti-class II CRAb. II. Retrospective study of HIV 1-infected hemophiliacs, suggest that patients with high titers of CRAb early in the disease progressed faster to full blown disease.
Blackburn
R
R
Division of Virology, NCI, NIH, Bethesda, Maryland 20892.
Clerici
M
M
Mann
D
D
Lucey
D R
DR
Goedert
J
J
Golding
B
B
Shearer
G M
GM
Golding
H
H
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000096:biosynthesis*; D003429:Cross Reactions; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006681:HLA-D Antigens / Q000737:chemistry*; D006801:Humans; D007108:Immune Tolerance; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D001323:Autoantibodies; D015700:HIV Envelope Protein gp41; D006681:HLA-D Antigens