Restricted and conserved T-cell repertoires involved in allorecognition of class II major histocompatibility complex.
The nature of the alloreactive T-cell response is not yet clearly understood. These strong cellular responses are thought to be the basis of allograft rejection and graft-vs.-host disease. The question of the extent of responding T-cell repertoires has so far been addressed by cellular cloning, often combined with molecular T-cell receptor (TCR) analysis. Here we present a broad repertoire analysis of primed responder cells from mixed lymphocyte cultures in which two different DR1/3 responders were stimulated with DR3/4 cells. Repertoire analysis was performed by TCR spectratyping, a method by which T cells are analyzed on the basis of the complementarity-determining region 3 length of different variable region (V) families. Strikingly, both responders showed very similar repertoires when the TCR V beta was used as a lineage marker. This was not seen when TCR V alpha was analyzed. A different pattern of TCR V beta was observed if the stimulating alloantigen was changed. This finding indicates that alloreactive T cells form a specific repertoire for each alloantigen. Since conservation appears to be linked to TCR V beta, the question of different roles of alpha and beta chains in allorecognition is raised.
De Palma
R
R
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee 53201-2178, USA.
Gorski
J
J
D002999:Clone Cells; D018076:DNA, Complementary / Q000235:genetics; D004277:DNA, Single-Stranded / Q000235:genetics; D006684:HLA-DR Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology*
D018076:DNA, Complementary; D004277:DNA, Single-Stranded; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell