TCR beta chain that forms peptide-independent alloreactive TCR transfers reduced reactivity with irrelevant peptide/MHC complex.
A major feature of the TCR repertoire is strong alloreactivity. Peptides presented by allogeneic MHC are irrelevant for recognition by a subset of alloreactive T cells. To characterize peptide-independent TCRs at the molecular level, we forced the expression of a TCRbeta chain isolated from a peptide-independent alloreactive CD8+ T cell line. The alloreactive TCR repertoire in the transgenic mouse was peptide dependent. However, analysis of essential TCR contacts formed during the recognition of self-MHC-restricted Ag showed that fewer contacts with peptide were established by the transgenic TCRbeta chain, and that this was compensated by additional contacts formed by endogenous TCRalpha chains. Thus, reduced interaction with the peptide appears to be a transferable feature of the peptide-independent TCRbeta chain. In addition, these findings demonstrate that reactivity to peptides is preferred over the reactivity to MHC during the formation of the TCR repertoire.
Santori
Fabio R
FR
Michael Heidelberger Division of Immunology, Department of Pathology and New York University Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Popmihajlov
Zoran
Z
Badovinac
Vladimir P
VP
Smith
Courtney
C
Radoja
Sasa
S
Harty
John T
JT
Vukmanović
Stanislav
S
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000502:physiology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D006183:H-2 Antigens; C110366:OVA-8; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin; D010047:Ovalbumin