The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dyall, R.
Right arrow Articles by Janetzki, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dyall, R.
Right arrow Articles by Janetzki, S.
The Journal of Immunology, 2000, 164: 1695-1698.
Copyright © 2000 by The American Association of Immunologists

MHC Polymorphism Can Enrich the T Cell Repertoire of the Species by Shifts in Intrathymic Selection

Ruben Dyall*, Ilhem Messaoudi*,{ddagger}, Sylvia Janetzki{dagger} and Janko Nikolic-ugic1,*,{ddagger}

* Laboratory of T Cell Development and {dagger} Swim Across America Laboratory, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and {ddagger} The Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021

The murine class I molecule H-2Kb and its natural gene conversion variant, H-2Kbm8, which differs from H-2Kb solely at 4 aa at the bottom of the peptide-binding B pocket, are expressed in coisogenic mouse strains C57BL/6 (B6) and B6.C-H-2bm8 (bm8). These two strains provide an excellent opportunity to study the effects of Mhc class I polymorphism on the T cell repertoire. We recently discovered a gain in the antiviral CTL repertoire in bm8 mice as a consequence of the emergence of the Mhc class I allele H-2Kbm8. In this report we sought to determine the mechanism behind the generation of this increased CTL diversity. Our results demonstrate that repertoire diversification occurred by a gain in intrathymic positive selection. As previously shown, the emergence of the same Mhc allele also caused a loss in positive selection of T cell repertoire specific for another Ag, OVA-8. This indicates that a reciprocal loss-and-gain pattern of intrathymic selection exists between H-2Kb and H-2Kbm8. Therefore, in the thymus of an individual, a new Mhc allele can select new T cell specificities, while abandoning some T cell specificities selected by the wild-type allele. A byproduct of this repertoire shift is a net gain of T cell repertoire of the species, which is likely to improve its survival fitness.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
A. Lang, J. D. Brien, I. Messaoudi, and J. Nikolich-Zugich
Age-Related Dysregulation of CD8+ T Cell Memory Specific for a Persistent Virus Is Independent of Viral Replication
J. Immunol., April 1, 2008; 180(7): 4848 - 4857.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. E. Tynan, N. A. Borg, J. J. Miles, T. Beddoe, D. El-Hassen, S. L. Silins, W. J. M. van Zuylen, A. W. Purcell, L. Kjer-Nielsen, J. McCluskey, et al.
High Resolution Structures of Highly Bulged Viral Epitopes Bound to Major Histocompatibility Complex Class I: IMPLICATIONS FOR T-CELL RECEPTOR ENGAGEMENT AND T-CELL IMMUNODOMINANCE
J. Biol. Chem., June 24, 2005; 280(25): 23900 - 23909.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. S. Block, Y. V. Mendez-Fernandez, V. P. Van Keulen, M. J. Hansen, K. S. Allen, A. L. Taboas, M. Rodriguez, and L. R. Pease
Inability of bm14 Mice to Respond to Theiler's Murine Encephalomyelitis Virus Is Caused by Defective Antigen Presentation, Not Repertoire Selection
J. Immunol., March 1, 2005; 174(5): 2756 - 2762.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
M. J. Miley, I. Messaoudi, B. M. Metzner, Y. Wu, J. Nikolich-Zugich, and D. H. Fremont
Structural Basis for the Restoration of TCR Recognition of an MHC Allelic Variant by Peptide Secondary Anchor Substitution
J. Exp. Med., December 6, 2004; 200(11): 1445 - 1454.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. S. Block, M. J. Hansen, V. P. Van Keulen, and L. R. Pease
MHC Class I Gene Conversion Mutations Alter the CD8 T Cell Repertoire
J. Immunol., October 15, 2003; 171(8): 4006 - 4010.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
W. A. Macdonald, A. W. Purcell, N. A. Mifsud, L. K. Ely, D. S. Williams, L. Chang, J. J. Gorman, C. S. Clements, L. Kjer-Nielsen, D. M. Koelle, et al.
A Naturally Selected Dimorphism within the HLA-B44 Supertype Alters Class I Structure, Peptide Repertoire, and T Cell Recognition
J. Exp. Med., September 2, 2003; 198(5): 679 - 691.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
I. Messaoudi, J. A. G. Patino, R. Dyall, J. LeMaoult, and J. Nikolich-Žugich
Direct Link Between mhc Polymorphism, T Cell Avidity, and Diversity in Immune Defense
Science, November 29, 2002; 298(5599): 1797 - 1800.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. J. Penn, K. Damjanovich, and W. K. Potts
MHC heterozygosity confers a selective advantage against multiple-strain infections
PNAS, August 20, 2002; 99(17): 11260 - 11264.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
I. Messaoudi, J. LeMaoult, B. M. Metzner, M. J. Miley, D. H. Fremont, and J. Nikolich-Zugich
Functional Evidence That Conserved TCR CDR{{alpha}}3 Loop Docking Governs the Cross-Recognition of Closely Related Peptide:Class I Complexes
J. Immunol., July 15, 2001; 167(2): 836 - 843.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.