Dissection of Cross-Reactivities Using a Panel of H-2Ld Alloreactive T Cell Hybridomas

Autor: Minnie McMillan, Catherine C. Killion, Joseph M. Dadgari, Pei-Jia Chen
Rok vydání: 1995
Předmět:
Zdroj: Cellular Immunology. 164:81-89
ISSN: 0008-8749
DOI: 10.1006/cimm.1995.1145
Popis: In order to explore the role which class I structure plays in alloreactivity, we have generated L d -reactive T cell hybridomas by fusion of a dm2 anti-BALB/cJ MLR with the BW5147 cell line and examined their stimulation by the following class I molecules (α1/α2/ α3): L q , D q , dm1, LP d /L d /D d , L q /D q /L d , and Q10/Q10/L d . We found that their specificities differed in their patterns of cross-reactions and were reasonably representative of those present in the bulk population of MLR-generated CTLs. L d /L d /D d and Q10/Q10/L d stimulated the majority of the hybridomas, L q and dm1 were recognized by over half of the panel, and L q /D q /L d stimulated only modestly, while D q was not recognized by any hybridoma. Correlation of these observed reactivities with class I structure suggests that putative TCR contact residues may play a significant role in recognition when compared to the polymorphic amino acid residues which control pocket specificity and peptide binding. Specifically, L q and D q possess very similar or identical pockets, in contrast to those of dm1 and Q10. However, Q10 has identical TCR contact residues to L d , both on the α1 and α2 α helices, unlike D q which is mismatched on both helices. L q and dm1 are mismatched compared to L d on only one helix. Thus, a molecular rationale for the cross-reactions observed in this study involves the direct participation of residues of class I molecules in allorecognition.
Databáze: OpenAIRE