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.
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
D
D
Jaraquemada
R
R
Martin
S
S
Rosen-Bronson
M
M
Flerlage
H F
HF
McFarland
E O
EO
Long
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