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PMID: 7544393 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Identification of residues in the V domain of CD80 (B7-1) implicated in functional interactions with CD28 and CTLA4.

The Journal of experimental medicine ·Vol. 182 ·No. 3 ·1995-09-01 ·Pages 667-75

Fargeas CA, Truneh A, Reddy M, Hurle M, Sweet R, Sékaly RP

Abstract

The CD80 (B7-1) molecule is a 45-60-kD member of the immunoglobulin superfamily that is expressed on a variety of cell types of haematopoietic origin. CD80 can provide a critical costimulatory signal to T cells by interacting with the T cell surface molecule CD28. CD80 also binds to the CD28-related molecule CTLA4, which is expressed on activated T cells, Recently, additional ligands of CD28 and CTLA4 have been described in mice and humans. One of them, CD86 (B-70 or B7-2) was characterized at the molecular level. Although similar in predicted structure to CD80, it is distantly related in amino acid sequence. In this study, human CD80 mutants were generated and tested for their ability to maintain the interaction with CD28 leading to adhesion and enhanced IL-2 production. Two hydrophobic residues in the V-like domain of CD80 were identified as critical for binding to CD28 and are also important for the interaction with CTLA4. These residues are adjacent to the epitope of the BB1 antibody, which inhibits CD28-CD80 interactions. One of these residues, Y87, is conserved in all CD80 and CD86 cloned from various species. These results being to unravel the structural requirements for binding to CD28 and CTLA4.

MeSH Terms
Abatacept Amino Acid Sequence Animals Antigens, CD Antigens, Differentiation/metabolism B7-1 Antigen/chemistry,metabolism Base Sequence CD28 Antigens/metabolism CTLA-4 Antigen Humans Immunoconjugates Interleukin-2/biosynthesis Lymphocyte Activation/physiology Mice Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Protein Binding Protein Conformation Sequence Alignment Species Specificity Structure-Activity Relationship Tryptophan/physiology Tyrosine/physiology
Chemicals
Antigens, CD Antigens, Differentiation B7-1 Antigen CD28 Antigens CTLA-4 Antigen CTLA4 protein, human Ctla4 protein, mouse Immunoconjugates Interleukin-2 Tyrosine Abatacept Tryptophan
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fargeas C A
Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Québec, Canada.
Truneh A
Reddy M
Hurle M
Sweet R
Sékaly R P
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.182.3.667
Published
1995-09-01
Pages
667-75
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192168
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.182.3.667 PMC Full Text View journal details
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