Proteins of Human Immunodeficiency Virus that Cross-React with Human 'Self' Antigens

: AIDS is caused by the human immunodeficiency virus (HIV) and constitutes a major health hazard to military and civilian populations. Our goal with this contract is to understand pathogenesis and to obtain a rational strategy for developing a vaccine by dissecting the humoral and cellular immune responses to infection by HIV against both the virus and host (self) antigens. With our initial two year grant we defined the immunodominant domain of HIV-1 and HIV-2 for B cell (antibody) responses and fine mapped the minimal essential epitope to 7 amino acids segment: (aa6O3-609, HIV-1; aa597-603, HIV-2) both containing flanking cysteine residues. With the current (second) grant we have documented the essential contributions of the flanking cysteines and solved the two dimensional structure of this B cell epitope using NMR. Of murine monoclonal antibodies raised to HIV-1 Gp aa598-609, a few (7 of 51) also reacted with a novel astrocyte antigen. Conditions in which this novel antigen was expressed and the location in the brain where the greatest expression occurred were determined. Expression libraries were constructed and are under analysis for isolating the gene expressing this astrocyte antigen.