Overlap of direct and indirect alloreactive T-cell repertoires when MHC polymorphism is limited to the peptide binding groove.
The immune response to allogeneic-MHC molecules can be divided into two pathways based on the nature of the antigen. In the direct pathway, T cells respond to intact allogeneic MHC molecules, while in the indirect pathway T cells respond to allo MHC-derived peptides presented by self-MHC. The T-cell repertoire used in the direct and indirect alloresponse have not been compared in the same alloantigen system. Here, HLA-DR transgenic mice are used to compare the repertoires of T cells that respond to the same alloantigen through either the direct or the indirect pathway. Separate direct and indirect DR1 anti-DR4 T-cell lines were generated and the T cell repertoire was analyzed by molecular methods. The same six Vbeta families were involved in both direct and indirect cultures indicating a complete overlap in the Vbeta gene usage. A partial overlap at the clonotype level was observed as two identical clonotypic TCRs were observed in both direct and indirect cultures. Interestingly, the T cells observed in both cultures were public as the same TCRs were identified in cultures developed from independent mice. These results raise the prospect that immune suppression of selected T cells during allo-transplantation can simultaneously modulate direct and indirect alloreactivities.
Battaglia
Manuela
M
Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI 53201-2178, USA.
Gorski
Jack
J
D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells; D015798:HLA-DR1 Antigen / Q000276:immunology*; D015804:HLA-DR4 Antigen / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*
D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta