Sequence motifs important for peptide binding to the human MHC class I molecule, HLA-A2

Previous studies have indicated that most HLA-A2-binding peptides are 9 amino acid (aa) residues long, with a Leu at position 2 (P2), and a Val or Leu at P9. We compared the binding properties of different peptides by measuring the rate of dissociation of beta 2-microglobulin from peptide-specific H...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 149; no. 11; pp. 3580 - 3587
Main Authors:	Parker, KC, Bednarek, MA, Hull, LK, Utz, U, Cunningham, B, Zweerink, HJ, Biddison, WE, Coligan, JE
Format:	Journal Article
Language:	English
Published:	Bethesda, MD Am Assoc Immnol 01-12-1992 American Association of Immunologists
Subjects:	AIDS/HIV Amino Acid Sequence Antigens Antigens, Viral - chemistry Antigens, Viral - immunology Biological and medical sciences Cytomegalovirus - immunology Fundamental and applied biological sciences. Psychology Fundamental immunology Glycine - chemistry Histocompatibility antigens (hla, h-2 and other systems) HIV Antigens - immunology HIV-1 - immunology HLA-A2 Antigen - metabolism Humans In Vitro Techniques Influenza A virus - immunology Molecular immunology Molecular Sequence Data Peptides - chemistry Peptides - metabolism Structure-Activity Relationship Viral Matrix Proteins - chemistry Viral Matrix Proteins - immunology Human HLA-System Specificity Peptides Molecular interaction Class I histocompatibility antigen Aminoacid sequence β2-Microglobulin
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Summary:	Previous studies have indicated that most HLA-A2-binding peptides are 9 amino acid (aa) residues long, with a Leu at position 2 (P2), and a Val or Leu at P9. We compared the binding properties of different peptides by measuring the rate of dissociation of beta 2-microglobulin from peptide-specific HLA-A2 complexes. The simplest peptide that we identified that could form HLA-A2 complexes had the sequence (in single letter aa code) GLFGGGGGV, indicating that three nonglycine aa are sufficient for binding to HLA-A2. To determine whether most nonapeptides that contained Leu at P2 and Val or Leu at P9 could bind to HLA-A2, we tested the binding of nonapeptides selected from published HIV and melanoma protein sequences, and found that six of seven tested formed stable HLA-A2 complexes. We identified an optimal antigenic undecapeptide from the cytomegalovirus gB protein that could form stable HLA-A2 complexes that contained apparent anchor residues at P2 and P11 (sequence FIAGN-SAYEYV), indicating that the spacing between anchor residues can be somewhat variable. Finally, we tested the importance of every aa in the influenza A matrix peptide 58-66 (sequence GILGFVFTL) for binding to HLA-A2, by using Ala-substituted and Lys-substituted peptides. We found that multiple positions were important for stable binding, including P2, P3, P5-P7, and P9. We conclude that the P2 and P9 anchor residues are of prime importance for peptide binding to HLA-A2. However, other peptide side chains (especially at P3) contribute to the stability of the interaction. In certain cases, the optimal length for peptide binding can be longer than 9 residues.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.149.11.3580