A rare cryptic translation product is presented by Kb major histocompatibility complex class I molecule to alloreactive T cells. J Exp Med 1995 Dec 01;182(6):1739-50
Date
12/01/1995Pubmed ID
7500018Pubmed Central ID
PMC2192241DOI
10.1084/jem.182.6.1739Scopus ID
2-s2.0-0028817871 (requires institutional sign-in at Scopus site) 63 CitationsAbstract
The identity of allogeneic peptide/major histocompatibility complex (MHC) complexes that elicit vigorous T cell responses has remained an interesting problem for both practical and theoretical reasons. Although a few abundant MHC class I-bound peptides have been purified and sequenced, identifying the unique T cell-stimulating peptides from among the thousands of existing peptides is still a very difficult undertaking. In this report, we identified the antigenic peptide that is recognized by an alloreactive bm1 anti-B6 T cell clone using a novel genetic strategy that is based upon measurement of T cell receptor occupancy in single T cells. Using lacZ-inducible T cells as a probe, we screened a splenic cDNA library in transiently transfected antigen-presenting cells (APCs) and isolated a cDNA clone that allowed expression of the appropriate peptide/Kb MHC complex in APC. The antigenic octapeptide (SVVEFSSL) exactly matched the consensus Kb MHC motif, but was surprisingly encoded by a non-ATG defined translation reading frame. Furthermore, the abundance of the naturally processed analog in untransfected cells was estimated to be <10 copies per cell. These results illustrate a novel strategy for identifying T cell-stimulating antigens in general and directly show that alloreactive T cells can respond to rather rare peptide/MHC complexes. These results also suggest that the total pool of processed peptides expressed on the APC surface may include those generated by cryptic translation of normally expressed transcripts.
Author List
Malarkannan S, Afkarian M, Shastri NAuthor
Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Antigen-Presenting Cells
Base Sequence
Cells, Cultured
DNA Primers
H-2 Antigens
Isoantigens
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Oligopeptides
T-Lymphocytes
Tubulin