AEGiS-07IAC: Molecular mimicry between HIV-1 gp41 and HLA class II: correlation between the generation of crossreactive antibodies, T cell function, and disease progression in infected individuals.

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

Molecular mimicry between HIV-1 gp41 and HLA class II: correlation between the generation of crossreactive antibodies, T cell function, and disease progression in infected individuals.

Int Conf AIDS 1991 Jun 16-21; 7:25 (abstract no. M.A.16)
Golding H, Clerici M, Mann D, Shearer GM, Blackburn R; Division of Virology, FDA, Bethesda, MD, USA

Two highly homologous sequences were found in conserved regions of HIV-1 gp41 (aa837-844), and human HLA class II beta chains (aa19-25). Early study demonstrated that 35% of HIV-1 infected individuals produce antibodies against the gp41 sequence which crossreact with HLA class II bearing cells (CRAb). Such CRAb could block in vitro proliferative responses of CD4+ T cells, and kill class II+ cells via Ab dependent cellular cytotoxicity (ADCC).

OBJECTIVES: (a) To correlate in asymptomatic patients (#CD4 cells greater than 500/ml) the presence of CRAb with their T cell function. (b) To determine in a retrospective study of HIV-1 infected hemophiliacs, if production of anti-class II CRAb affect the rate of progression to AIDS.

METHODS: 1) Patients' sera were tested by ELISA for reactivity against the gp41 and class II derived homologous peptides. 2) PBL from stage 1+2 AIDS patients, were tested for their ability to proliferate and produce IL2 in response to recall antigens (flu/tetanus), allogeneic stimuli, and PHA. 3) The #CD4+ cells and clinical status of patients were followed routinely.

RESULTS: (a) 50% of asymptomatic patients demonstrated a selective early loss of their CD4 dependent T cell resposes to recall antigens, while still responding to PHA and allogeneic stimuli. Interestingly, the presence of CRAb in patients' sera correlated closely (p less than 0.001) with their lack of responses to flu/tetanus. (b) HIV-1 infected hemophiliacs producing high titers of CRAb early in the disease, progressed faster to full blown disease.

CONCLUSIONS: The two studies in concert, suggest that the early appearance of anti-class II autoantibodies as a result of the molecular mimicry between HIV 1 gp41 and self HLA antigens, may be a factor in the prognosis of HIV-1 infected individuals.

Keywords: AEGIS, HIV-1, Disease Progression, T-Lymphocytes, Molecular Mimicry, Antibodies, HLA Antigens, Acquired Immunodeficiency Syndrome, Autoantibodies, Antigens, CD4, HLA-D Antigens, Phytohemagglutinins, Retrospective Studies, Human, In Vitro, physiology, genetics, ICA7
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