Sequence homology between acquired immunodeficiency syndrome virus envelope protein and interleukin 2.

Abstract

[9188][9189][9190][9191][9192], the authors request that the following be noted. The last paragraph on p. 9188 should read: "Others have obtained experimental evidence indicating that the region of IL-2 that contains peptide IL2-A is important for activity. Ju et al. (25) used site-directed mutagenesis to determine that residues 21-40 of IL-2 (residues 1-20 of the mature protein) form one of the regions of IL-2 required for full biological activity and that this region is recognized by neutralizing anti-IL-2 antibodies. Chizzonite et al. (24) Communicated by William A. Goddard III, August 8, 1986 ABSTRACT A region of homology has been found between the envelope (env) protein of the acquired immunodeficiency syndrome (AIDS) virus and a portion of interleukin 2 (IL-2) that purportedly binds to the IL-2 receptor. This homology, between two proteins associated with opposing biological functions, suggests possible mechanisms for the immunosuppressive activity of the AIDS virus. Two mechanisms are proposed in which the AIDS virus env protein interferes with IL-2 activity either directly or indirectly. A region of similarity to the purported IL-2 receptor binding site on IL-2 and AIDS virus env is present in the env proteins of other retroviruses associated with immunosuppression. A synthetic peptide vaccine for AIDS is suggested based on the IL-2 receptor binding sequence in AIDS virus env.

B Cell Epitope Mapping of Human Immunodeficiency Virus Envelope Glycoproteins with Long (19- to 36-residue) Synthetic Peptides

“…This bias of human anti-HIV-1 towards recognition of peptides from the HIV-1 gpl20 and gp41 sequences probably cannot be ascribed to regions of homology between the virus glycoproteins and human host proteins. For example, peptide 808-845, sharing a region of homology with the human major histocompatibility complex class II peptide fl-domain (Golding et al, 1988) and peptides 411-445 and 38-61, sharing homology with the human immunoglobulin heavy chain constant region (Maddon et al, 1986) were not recognized by human anti-HIV-l. On the other hand, peptide 845-862 sharing homology with human interleukin 2 (Reiher et al, 1986) and peptide 61-90 sharing homology with the human immunoglobulin heavy chain constant region (Maddon et al, 1986) are recognized by human anti-HIV-1.…”

“…Partial sequence homology between distinct segments of HIV-1 env glycoproteins and domains of functionally important host proteins suggested that immunization with the entire gpl20 + gp41 sequence may elicit harmful autoimmune responses (Maddon et al, 1986;Reiher et al, 1986;Golding et al, 1988;Brenneman et al, 1988). Selected regions from HIV-1 gpl20 and gp41 glycoproteins have immunosuppressive effects, suppress lymphocyte blastogenic responses and inhibit the activity of natural killer cells (Klasse et al, 1988;Nair et al, 1988;Cauda et al, 1988).…”

Common epitope in human immunodeficiency virus (HIV) I-GP41 and HLA class II elicits immunosuppressive autoantibodies capable of contributing to immune dysfunction in HIV I-infected individuals.

“…Thus, in addition to its direct cytopathic effects on human T helper cells, HIV-I, similar to other infectious agents (1, 2, 11), contains several epitopes which closely mimic self proteins (4, 12,13 …”

Pathogenesis of Human Immunodeficiency Virus Infection

“…In this regard, similarities between HIV proteins and normal cellular proteins could elicit antiviral antibodies or cellular immune responses that crossreact with normal cells (74,868) (Table 31). Evidence in favor of this possibility includes the presence of IL-1, IL-2 receptor, MHC class I and class II, and interferon-like sequences in the HIV genes, as well as potential crossreacting epitopes on certain envelope portions of the virus (224,351,382,383,667,668,839,979). Moreover, crossreactive antibodies recognizing a platelet glycoprotein and an HIV gpl20 epitope have been cited as a possible mechanism for thrombocytopenia (70a).…”