HIV env glycoprotein shares a cross‐reacting epitope with a surface protein present on activated human monocytes and involved in antigen presentation

Abstract

A serological cross-reactivity between env gp120 glycoprotein of the human immunodeficiency virus (HIV) and a human cellular surface protein has been defined by a monoclonal antibody (M38) raised against HIV. The cellular antigen is a protein of ca. 80 kDa expressed on a small fraction of mononuclear cells in peripheral blood and in lymph nodes. The protein behaves as an activation antigen of the monocytic lineage since it is expressed by monocytes in plastic-adherent culture conditions and by interferon-gamma-treated monocytes and pro-monocytic U937 cells. The protein is involved in antigen presentation since the antibody efficiently inhibits the proliferation of responsive lymphocytes in autologous tetanus toxoid presentation assays. In the T lymphoblastoid line H9, the protein is present in very small amounts, is not induced by interferon-gamma and increases after HIV infection. Sera from lymphoadenopathy syndrome and acquired immunodeficiency syndrome (AIDS) patients fail to detect the cellular protein, although containing antibodies reacting with gp120. We propose that both viral and cellular structures recognized by the monoclonal antibody (mAb) are involved in interactions with CD4 molecules of T helper lymphocytes and that such molecular mimicry might be relevant in the pathology of HIV infection. This view is supported by the finding that BL/10T4, a CD4-specific mAb, binds to M38 neutralizing its interactions with HIV and with monocytes. mAb M38 thus behaves as the internal image of CD4. This single property would explain all its diverse binding characteristics.

Relative Expression Levels of the HLA Class-I Proteins in Normal and HIV-Infected Cells

“…Monoclonal antibodies (mAb) that bind HLA were characterized for reactivity against 97 common HLA class-I alleles using commercially available beads coated with individual HLA allotypes as previously described [28]. Of numerous antibodies screened, the following were used for further analyses: purified mAbs W6/32 [29], BBM.1 [30] and L31 [31] purchased from Serotec, Santa Cruz Biotechnology and MediaPharma, respectively; hybridoma supernatants of mAbs PA2.1 [32] and 22E-1 [33,34] generously supplied by Drs. N. Holmes and I. Smith; mAb DT9 [14,35] purified from supernatant of a hybridoma kindly provided by Dr. V. Braud.…”

HLA-C increases HIV-1 infectivity and is associated with gp120

“…The L31 monoclonal antibody is specific for the α domain of HLA-C heavy chain [32-34], not associated to β 2 -microglobulin. Anti-gp120 human sera from HIV-positive patients were kindly provided by Dr. Lucia Lopalco, DIBIT-HSR, Milan, Italy.…”

Epitopes of Human Immunodeficiency Virus Regulatory Proteins <i>Tat</i><i>,</i><i>Ne</i><i>f</i> and <i>Rev</i> are Expressed in Skin in Atopic Dermatitis

“…Skin in atopic dermatitis, especially after epi cutaneous allergen patch testing, shows an additional ex pression of such epitopes. It remains to be established whether this expression reflects the presence of as yet un known endogenous retroviral(-Iikc) elements [7][8][9], or represents molecular mimicry of conformational epitopes shared by viral and host molecules [10][11][12][13]. Fundamental studies on this aspect may broaden the present insight in host-retrovirus interactions.…”

“…It was hypothesized that the binding can be ascribed to the expression of as yet unknown endogenous retroviral(-like) elements [7][8][9], or on molecular mimicry of conformational epitopes shared by viral and host molecules [10][11][12][13].…”