Cytotoxic T lymphocyte (CTL) activation requires specific T cell receptor (TCR)-class I major histocompatibility complex (MHC) antigen complex interactions as well as the participation of coreceptor or accessory molecules on the surface of CTL. CD8 can serve as a coreceptor in that it binds to the same MHC class I molecules as the TCR to facilitate efficient TCR signaling. In addition, CD8 can be "activated" by TCR stimulation to bind to class I molecules with high avidity, including class I not recognized by the TCR as antigenic complexes (non-antigen [Ag] class I), to augment CTL responses and thus serve an accessory molecule function. A Glu/Asp227-->Lys substitution in the class I alpha 3 domain acidic loop abrogates lysis of target cells expressing these mutant molecules by alloreactive CD8-dependent CTL. Lack of response is attributed to the destruction of the CD8 binding site in the alpha 3 domain which is likely to disrupt CD8 coreceptor function. The relative importance of the class I alpha 3 domain acidic loop Glu227 in coreceptor as opposed to accessory functions of CD8 is unclear. To address this issue, we examined CTL adhesion and degranulation in response to immobilized class I-peptide complexes formed in vitro from antigenic peptides and purified class I molecules containing wild-type or Glu227-->Lys substituted alpha 3 domains. The alpha 3 domain mutant class I-peptide complexes were bound by CTL and triggered degranulation, however to much lower levels than wild-type class I-peptide complexes. In further experiments, it is directly demonstrated that the alpha 3 domain mutant class I molecules, which lack the Glu227 CD8 binding site, still serve as TCR-activated, avidity-enhanced CD8 accessory ligands. However, mutant class I peptide Ag complexes failed to effectively serve as CD8 coreceptor ligands to initiate TCR-dependent signals required to induce avidity-enhanced CD8 binding to coimmobilized non-Ag class I molecules. Thus the Glu227-->Lys mutation effectively distinguishes CD8 coreceptor and avidity-enhanced CD8 accessory functions.
Skip Nav Destination
Article navigation
1 November 1996
Article|
November 01 1996
Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions.
L Shen,
L Shen
Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Search for other works by this author on:
T A Potter,
T A Potter
Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Search for other works by this author on:
K P Kane
K P Kane
Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Search for other works by this author on:
L Shen
Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
T A Potter
Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
K P Kane
Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (5): 1671–1683.
Citation
L Shen, T A Potter, K P Kane; Glu227-->Lys substitution in the acidic loop of major histocompatibility complex class I alpha 3 domain distinguishes low avidity CD8 coreceptor and avidity-enhanced CD8 accessory functions.. J Exp Med 1 November 1996; 184 (5): 1671–1683. doi: https://doi.org/10.1084/jem.184.5.1671
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement