Molecular basis for the high affinity interaction between the thymic leukemia antigen and the CD8alphaalpha molecule.
The mouse thymic leukemia (TL) Ag is a nonclassical MHC class I molecule that binds with higher affinity to CD8alphaalpha than CD8alphabeta. The interaction of CD8alphaalpha with TL is important for lymphocyte regulation in the intestine. Therefore, we studied the molecular basis for TL Ag binding to CD8alphaalpha. The stronger affinity of the TL Ag for CD8alphaalpha is largely mediated by three amino acids on exposed loops of the conserved alpha3 domain. Mutant classical class I molecules substituted with TL Ag amino acids at these positions mimic the ability to interact with CD8alphaalpha and modulate lymphocyte function. These data indicate that small changes in the alpha3 domain of class I molecules potentially can have profound physiologic consequences.
Attinger
Antoine
A
La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Devine
Lesley
L
Wang-Zhu
Yiran
Y
Martin
Donald
D
Wang
Jia-Huai
JH
Reinherz
Ellis L
EL
Kronenberg
Mitchell
M
Cheroutre
Hilde
H
Kavathas
Paula
P
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D016827:CD8 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D006801:Humans; D006825:Hybridomas; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C028388:thymus-leukemia antigens; D004247:DNA