The CD8 coreceptor interaction with the α3 domain of HLA class I is critical to the differentiation of human cytotoxic t-lymphocytes specific for HLA-A2 and HLA-Cw4

Pamela K. Wesley, Carol Clayberger, Shu cchen Lyu, Alan M. Krensky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The CD8 coreceptor interacts with MHC class I molecules through an acidic loop in the MHC α3 domain. Mutations in this region reduced binding between cells expressing mutant HLA molecules and CHO cells transfected with CD8 α chain, with mutations at residue 227 having the greatest effects. This study was undertaken to examine the role of the CD8-HLA interaction in the generation of primary and long-term CTLs. HLA-A*0201 genes (wild type or mutated at residue 227) were transfected into a cell line that lacked expression of HLA-A or B molecules but expressed HLA-Cw4. These cells were used as stimulators for PBLs from a normal donor. Cultures were tested for cytotoxicity at various times thereafter. Transfectants expressing the HLA-A*0201 mutant gene were poor stimulators of primary HLA-A2-specific CTLs. In long-term culture, HLA-Cw4-specific CTLs predominated, indicating that continuous expansion of allogeneic CTLs depends upon an efficient CD8-MHC class I interaction.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalHuman Immunology
Volume36
Issue number3
DOIs
StatePublished - Mar 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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