Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains.
Murine monoclonal antibodies (mAbs) M38 and L31 define two epitopes of a surface protein of activated lymphocytes and monocytes. It has been shown that M38 also defines a crossreactive epitope of human immunodeficiency virus type 1 (HIV-1) gp120 (Beretta et al., 1987. Eur. J. Immunol. 17: 1793). The mAb inhibits syncytia formation driven by HIV-1-infected cells. The surface protein was demonstrated to be a class I MHC alpha chain, by sequence analysis of the corresponding cDNA and by immunological means. The epitopes defined by mAbs M38 and L31 are monomorphic and hidden (i.e., inaccessible to antibodies) on native HLA molecules expressed by resting cells, but can be evidenced on denatured proteins by Western blot analysis. The two epitopes become accessible after activation processes have been implemented, likely reflecting a conformational alteration of alpha chains (such as that described by Schnabl et al. 1990. J. Exp. Med. 171:1431). Consistent with molecular data are the results of functional analysis, which indicate that the molecule recognized by M38 and L31 is a gate for pleiotropic negative signals, since the two mAbs were shown to inhibit monocyte antigen presentation and lymphocyte mitogenic proliferation, respectively.
Grassi
F
F
Dipartimento di Biologia e Genetica per le Scienze Mediche, Università di Milano, Italy.
Meneveri
R
R
Gullberg
M
M
Lopalco
L
L
Rossi
G B
GB
Lanza
P
P
De Santis
C
C
Brattsand
G
G
Buttò
S
S
Ginelli
E
E
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003429:Cross Reactions; D004247:DNA / Q000235:genetics; D000939:Epitopes / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D021382:Protein Sorting Signals; D004247:DNA