Random association between the peptide repertoire of A2.1 class I and several different DR class II molecules

• Published in: The Journal of immunology (1950) Vol. 147; no. 11; pp. 3893 - 3900
• Main Authors: Sette, A, Vitiello, A, Farness, P, Furze, J, Sidney, J, Claverie, JM, Grey, HM, Chesnut, R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.12.1991; American Association of Immunologists
• Subjects: AIDS/HIV; Amino Acid Sequence; Antigens; Antigens, Viral - chemistry; Antigens, Viral - immunology; beta 2-Microglobulin - metabolism; Biological and medical sciences; Cytotoxicity, Immunologic; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hepatitis B virus - immunology; Herpesvirus 4, Human - immunology; Histocompatibility antigens (hla, h-2 and other systems); HIV Antigens - immunology; HIV Antigens - metabolism; HLA-A2 Antigen - immunology; HLA-A2 Antigen - metabolism; HLA-DR Antigens - immunology; HLA-DR Antigens - metabolism; Humans; In Vitro Techniques; Molecular immunology; Molecular Sequence Data; Peptides - immunology; Peptides - metabolism; Structure-Activity Relationship; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured; Viral Proteins - immunology; Viral Proteins - metabolism; Antigen; Human; Binding capacity; Synthetic product; Antigenic determinant; Peptides; Major histocompatibility system; Class II histocompatibility antigen; HLA-DR-locus; Molecular interaction; Self non self recognition; Class I histocompatibility antigen
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.147.11.3893

The interaction between synthetic peptides and A2.1 class I MHC molecules has been investigated using an inhibition of Ag presentation assay and unbiased peptide sets derived of either viral or eucaryotic origin. For the various sets, strong binding (defined as significant inhibition at the 30 micrograms/ml level) was detected in 7 to 46% of the peptides tested, with an overall frequency of 26%. A set of self-peptides derived from human beta 2 microglobulin was also included in the study. In this case, strong binding was detected in 3 of 15 peptides (20%), thus formally demonstrating a lack of self-/non-self-discrimination at the level of class I molecules. When the whole A2.1-binding database of 105 peptides thus generated was examined by sequence analysis, a significant correlation was found with a recently proposed A2.1-binding motif, whereas no particular positive or negative association was detected between the capacity to bind A2.1 and three different class II alleles (DR1, DR5, and DR7). Finally, using this approach, several peptides capable of binding both A2.1 and multiple DR alleles have been identified, suggesting possible candidates for development of peptide vaccines eliciting both class I and class II restricted responses.