BINDING ANALYSIS OF 95 HIV GP120 PEPTIDES TO HLA-DR1101 AND HLA-DR0401 EVIDENCED MANY HLA-CLASS-II BINDING REGIONS ON GP120 AND SUGGESTED SEVERAL PROMISCUOUS REGIONS

To identify HLA-DR-binding peptides within the human immunodeficiency virus (HIV)-1 proteins, 95 overlapping synthetic peptides representing the entire sequence of gp120-LAI were screened for their capacity to bind to two HLA-DR molecules with distant sequences (DR0401 and DR1101 ). By using a cell surface competitive binding assay, 56 DR-binding pe ptides were identified, of which 35 bound to both DR1101 and DR0401. A highly significant concordance was evidenced by statistical analysis between binding of peptides to one and to the other DR molecule, sugge sting a high proportion of promiscuity among gp120 peptides, even thou gh no clear sequence pattern accounting for such promiscuity was found . DR-binding peptides were located along the entire gp120 sequence. Ye t, the majority of them (42 among 56) were concentrated in seven multi agretopic regions that were arbitrarily defined as regions containing four or more overlapping continuous peptides binding to DR1101 and/or DR0401. A good correlation was found between DR-binding regions or DR- binding peptides defined in this study and promiscuous T helper gp120 epitopes previously described in seropositive individuals. All these r esults suggest that the identification of multiagretopic DR-binding re gions may be a great help for the predicition of protein determinants that have the likelihood of being promiscuous T helper epitopes in hum ans.