HLA-DR2a is the dominant restriction molecule for the cytotoxic T cell response to myelin basic protein in DR2Dw2 individuals.
The HLA-DR2 restriction of the T cell response to myelin basic protein (MBP) was studied using murine L cells transfected with DRalpha and either DR2a or DR2b beta-chain cDNA. DR2a and DR2b represent the two isotypic DRbeta chains expressed in DR2Dw2 haplotypes. Eleven MBP-specific cytolytic T cell lines derived from patients with multiple sclerosis were isolated. Two of these cell lines recognized MBP-pulsed DR2-expressing L cell transfectants and four of them could only recognize the L cells if the adhesion molecule ICAM-1 was expressed in addition to HLA-DR2. Five of the six lines were restricted by HLA-DR2a; one line recognized Ag in conjunction with DR2b, but only if ICAM-1 was coexpressed. The remaining five lines did not lyse MBP-pulsed L cells. The ability of the DR2b molecules on transfected cells to stimulate T cells was confirmed with DR2b-allospecific T cell clones. Although five MBP-specific lines were restricted by DR2a, they recognized different parts of the MBP molecule, as demonstrated by the presentation of shorter peptides. Thus, our results suggest that DR2a is a dominant restriction molecule in MBP-specific responses by DR2+ MS patients. The results also indicate that the reported heterogeneity in MBP epitopes recognized by DR2-restricted T cells, may not be due to the use of different restriction elements but rather to the binding of different MBP peptides to DR2a molecules.
Jaraquemada
D
D
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
Martin
R
R
Rosen-Bronson
S
S
Flerlage
M
M
McFarland
H F
HF
Long
E O
EO
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D015802:HLA-DR2 Antigen / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007739:L Cells; D008213:Lymphocyte Activation; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D001324:Autoantigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; D015802:HLA-DR2 Antigen; D004676:Myelin Basic Protein; D018799:Intercellular Adhesion Molecule-1