Requirement for Q226, but not multiple charged residues, in the class I MHC CD loop/D strand for TCR‐activated CD8 accessory function

• Published in: European journal of immunology Vol. 33; no. 3; pp. 676 - 684
• Main Authors: Durairaj, Micheal, Sharma, Ranjana, Varghese, Jay C., Kane, Kevin P.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.03.2003
• Subjects: Adhesion molecule; Animals; CD8; CD8 Antigens - physiology; Cell Adhesion; Cell Degranulation; CTL; Dimerization; Histocompatibility Antigens Class I - chemistry; Histocompatibility Antigens Class I - physiology; MHC; Mice; Mice, Inbred C57BL; Receptors, Antigen, T-Cell - physiology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - physiology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200323499

Activation of CD8+ cytotoxic T lymphocytes typically begins with recognition of class I MHC‐peptide complexes by the TCR and CD8 as a coreceptor. In its coreceptor role, CD8 binds thesame class I‐peptide antigen complex as the TCR, enhancing the strength of TCR‐class I interaction. Subsequent to initial TCR engagement, CD8 acts as an accessory molecule by binding any properly conformed class I molecules on the target cell surface, leading to CD8‐mediated adhesion and cosignaling functions. We expressed and isolated a number of mutant class I molecules in which one or moreacidic or polar residues in the class I α3 domain CD loop and D strand region, or α2 domain were altered. Using solid phase CTL adhesion and degranulation assays with isolated class I molecules, we demonstrate that multiple acidic residues in the α3 domain, although involved in CD8 coreceptor interaction, are not required for TCR‐activated CD8 accessory interactions. Instead, we show that Q226, a polar group on the end of the CD loop, is required for TCR‐activated CD8 accessory functions. These results indicate that CD8 coreceptor and accessory interactions differ substantially and suggest that TCR activation results in changes that alter the structural constraints for CD8 accessory interactions.