Multiple class I motifs revealed by sequencing naturally processed peptides eluted from rat T cell MHC molecules.
Class I major histocompatibility complex (MHC) molecules interact with a diverse array of self and foreign peptides. Displayed on the cell surface, the class I/peptide complex provides an extracellular indication of the intracellular milieu. We have characterized the Lewis rat Vbeta8.2+ T cell hybridoma C14/BW12-12A1 by FACS analysis and have used immunoaffinity chromatography to purify class I molecules from these cells. Peptides eluted from the class I molecules have been fractionated by HPLC and sequenced. Self-peptide mixtures indicate two distinct peptide motifs, suggesting the possibility of multiple class I loci. The majority of the naturally processed peptide ligands were nonamers. Naturally processed peptide ligands fitting the first motif contained a hydrophobic leucine anchor residue at position three and a carboxyl-terminal serine anchor residue. A second motif was characterized by a tyrosine or phenylalanine residue at position three and a phenylalanine or isoleucine carboxyl-terminal residue. Four peptides derived from the Vbeta8.2 T cell receptor have sequences that fit these motifs, providing a mechanistic explanation for their immunoregulatory role. Identification of these class I peptide binding motifs will be useful for predicting potential CTL epitopes in studies on autoimmunity, immunoregulation and transplantation in the Lewis rat.
Burrows
G G
GG
Department of Neurology, Oregon Health Sciences University, Portland 97201, USA. ggb@antigen.ohsu.edu
Ariail
K
K
Celnik
B
B
Gambee
J E
JE
Offner
H
H
Vandenbark
A A
AA
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes / Q000737:chemistry; D005805:Genes, MHC Class I; D006649:Histocompatibility Antigens / Q000737:chemistry* / Q000235:genetics; D006825:Hybridomas / Q000737:chemistry; D008024:Ligands; D010446:Peptide Fragments / Q000737:chemistry* / Q000302:isolation & purification; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D017421:Sequence Analysis
D000939:Epitopes; D006649:Histocompatibility Antigens; D008024:Ligands; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C038353:histocompatibility antigens RT, rat