THE RAT CIM EFFECT - TAP ALLELE-DEPENDENT CHANGES IN A CLASS-I MHC ANCHOR MOTIF AND EVIDENCE AGAINST C-TERMINAL TRIMMING OF PEPTIDES IN THEER

Functional polymorphism in the rat peptide transporter associated with antigen processing (TAP) changes the peptide pool available for bindi ng and presentation by a class I MHC allele, RT1.A(a). The peptide bin ding motif for RT1.A(a), determined by stabilization with synthetic pe ptides, included a strong preference for arginine at the peptide C ter minus. Analysis of natural peptides bound to RT1.A(a) by both pool seq uencing and anhydrotrypsin chromatography revealed that TAP polymorphi sm determined the presence or absence of arginine as the peptide C-ter minal residue. This result highlights the in vivo impact of TAP-peptid e selectivity, and provides evidence against a high rate of generation of new C termini by protease activity in the endoplasmic reticulum.