Many peptide fragments of alien antigens are homologous with host proteins, thus canalizing T-cell responses.
All proteins of this world are constructed in compliance with the same rule. Accordingly, two totally unrelated proteins, on the average, share 30 identical tripeptides, two tetrapeptides, and one pentapeptide per 500 residues. With this in mind, the 221-residue-long influenza virus hemagglutinin II (IVHA-II), as a representative of alien antigens, was compared with three diverse proteins representing the host: 533-residue-long chicken c-src protein kinase (c-src product of the cellular oncogene of Rous sarcoma virus), 595-residue-long human estrogen receptor, and 585-residue-long human serum albumin. Forty-three tripeptides, two tetrapeptides, and one pentapeptide of IVHA-II were also found in one or the other of the three host proteins. Six regions of IVHA-II (9-22 residues long) in which oligopeptides were clustered that were identical to their host oligopeptides were defined as "host-homologous" regions, and the remaining regions were called "nonself" or "pathogen-specific" regions. Because the total number of host proteins is vastly more than three, host-homologous regions were no doubt underestimated, while only one or two regions of IVHA-II must remain as truly pathogen-specific. Nevertheless, oligopeptide analysis of two known T-cell response-eliciting peptide fragments and one known inert peptide fragment of a virus and a malarial protozoan readily revealed the latter to be a host-homologous region. Of the two known T-cell response-eliciting peptide fragments, one was more nonself than the other. Not surprisingly, the more nonself fragment elicited helper T-cell response from individuals of diverse major histocompatibility complex haplotypes, whereas the less nonself fragment elicited cytotoxic T-cell response only from HLA-A2 human individuals.
Ohno
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Beckman Research Institute of the City of Hope, Duarte, CA 91010-0269.
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000276:immunology; D015800:Protozoan Proteins; D011960:Receptors, Estrogen / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012709:Serum Albumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
D000953:Antigens, Protozoan; D006389:Hemagglutinins, Viral; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D012709:Serum Albumin; D014763:Viral Matrix Proteins; C041595:circumsporozoite protein, Protozoan; D016392:Proto-Oncogene Proteins pp60(c-src)