HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Byers, D. E. Articles by Lindahl, K. F. Search for Related Content PubMed PubMed Citation Articles by Byers, D. E. Articles by Lindahl, K. F.

Peptide Affinity and Concentration Affect the Sensitivity of M3-Restricted CTLs Induced In Vitro¹

Howard Hughes Medical Institute, Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235

In vitro stimulation of mouse splenocytes with hemagglutinin (HA) 173–190, a peptide derived from influenza virus hemagglutinin (A/JAP/305/57, H2N2), induces CTLs that are directed to the MHC class Ib molecule, H2-M3. M3 preferably binds peptides bearing an N-terminal formylmethionine. In this study, we show that several related nonformylated peptides can induce anti-HA CTLs in vitro: MLIIW (the minimal epitope), derived from HA186–190 at the C-terminal end of HA173–190; MLIIWG; MLIIWGV; and MLIIWGI, as well as formylated MLIIW. The heptamer peptides correspond to a polymorphism of HA192 in H2 strains of influenza; they have the highest relative affinities for M3 of the nonformylated peptides and higher affinities than some formylated mitochondrial peptides. Depending on the affinity of the peptide, a range of concentrations can be used to induce CTLs. One nanomolar of the high affinity f-MLIIW peptide can induce anti-HA CTLs, whereas 100-fold more of the lower affinity MLIIW peptide is needed. Lines induced with high concentrations (1 µM or greater) of f-MLIIW recognize Ag poorly, and the most efficient CTLs are induced with the lowest concentrations of peptide. Analysis with a panel of anti-TCRVß Abs shows that different T cells respond to high vs low peptide; the repertoire of cells responding to higher concentrations is more diverse, consistent with the expansion of more, but less efficient, clones. Thus, peptide affinity and concentration should be considered together for generating efficient antipeptide CTLs in vitro.

This article has been cited by other articles:

				M. Kim, H.-B. Moon, K. Kim, and K.-Y. Lee Antigen dose governs the shaping of CTL repertoires in vitro and in vivo Int. Immunol., March 1, 2006; 18(3): 435 - 444. [Abstract] [Full Text] [PDF]