Dual HLA class I and class II restricted recognition of alloreactive T lymphocytes mediated by a single T cell receptor complex.
The alloreactive human T cell clone MBM15 was found to exhibit dual specificity recognizing both an antigen in the context of the HLA class I A2 molecule and an antigen in the context of the HLA class II DR1. We demonstrated that the dual reactivity that was mediated via a single clonal T cell population depended on specific peptide binding. For complete recognition of the HLA-A2-restricted specificity the interaction of CD8 with HLA class I is essential. Interestingly, interaction of the CD8 molecule with HLA class I contributed to the HLA-DR1-restricted specificity. T cell clone MBM15 expressed two in-frame T cell receptor (TCR) Valpha transcripts (Valpha1 and Valpha2) and one TCR Vbeta transcript (Vbeta13). To elucidate whether two TCR complexes were responsible for the dual recognition or one complex, cytotoxic T cells were transduced with retroviral vectors encoding the different TCR chains. Only T cells transduced with the TCR Valpha1Vbeta13 combination specifically recognized both the HLA-A2(+) and HLA-DR1(+) target cells, whereas the Valpha2Vbeta13 combination did not result in a TCR on the cell surface. Thus a single TCRalphabeta complex can have dual specificity, recognizing both a peptide in the context of HLA class I as well as a peptide in the context of HLA class II. Transactivation of T cells by an unrelated antigen in the context of HLA class II may evoke an HLA class I-specific T cell response. We propose that this finding may have major implications for immunotherapeutic interventions and insight into the development of autoimmune diseases.
Heemskerk
M H
MH
Department of Hematology, Leiden University Medical Center, C2-R, P.O. Box 9600, 2300 RC Leiden, The Netherlands. m.h.m.heemskerk@lumc.nl
de Paus
R A
RA
Lurvink
E G
EG
Koning
F
F
Mulder
A
A
Willemze
R
R
van Rood
J J
JJ
Falkenburg
J H
JH
D016827:CD8 Antigens / Q000502:physiology; D003429:Cross Reactions; D015789:HLA-A2 Antigen / Q000276:immunology*; D015798:HLA-DR1 Antigen / Q000276:immunology*; D006801:Humans; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D016827:CD8 Antigens; D015789:HLA-A2 Antigen; D015798:HLA-DR1 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta