CLONAL ANALYSIS OF MURINE-B CELL RESPONSE TO THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)-GAG P17-ANTIGEN AND P25-ANTIGEN

The antigenicity of HIV-gag p17 and p25 proteins was analyzed using a panel of 52 monoclonal antibodies (mAb) derived from 17 independent fusion experiment protocols performed in 12 different laboratories. These mAb were tested for their capacity to bind peptides corresponding to sequences of HIVI-BRU-gag p17 and p25. Thirty-five overlapping peptides (P1 to P35) totally covering the pl7 and p25 proteins were used. This study allowed us to identify four immunodominant regions inducing B cell response, two on pl7 corresponding to P2 and P13 (amino acids 11-25 and 121-132, respectively) and two on p25 corresponding to P21 and P28-P29-P30 (a.a. 201-218 and 285-320 respectively). According to secondary structure predictions, peptides P2 and P21 contained hydrophilic alpha helix folded regions whereas P13 sequence presented a beta turn propensity. These regions and the P28-30 region were also predicted to be easily accessible to mAb. Several other p25-derived peptides: P15 (a.a. 142-156), P16 (a.a. 148-162), P19 (a.a. 176-192), P22 (a.a. 219 233) and P23 (a.a. 233-253) were recognized by mAb. No p17-derived peptide other than P2, P13 and P12 (a.a. 111-123) was found to react with mAb. Cross-blocking studies between mAb. suggested the existence of more than four distinct-epitopic areas on pl7 and eight on p25.