Acetylcholine receptor peptide recognition in HLA DR3-transgenic mice: In vivo responses correlate with MHC-peptide binding

Raghavan Pillai Raju, E. G. Spack, C. S. David

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

HLA DR3 is an MHC molecule that reportedly predisposes humans to myasthenia gravis (MG). Though MG is an Ab-mediated autoimmune disease, CD4+ T cells are essential for the generation of high-affinity Abs; hence the specificities of autoreactive CD4+ T cells are important. In this study we report the HLA DR3-restricted T cell determinants on the extracellular region sequence of human acetylcholine receptor α subunit. We find two promiscuous determinants on this region 141-160 and 171-190 as defined by their immunogenicity in HLA DR3-, HLA DQ8-, and HLA DQ6-transgenic mice in the absence of endogenous mouse class II molecules. We also studied the minimal determinants of these two regions by truncation analysis, and the MHC binding affinity of a set of overlapping peptides spanning the complete sequence region of human acetylcholine receptor α subunit. One of the peptide sequences strongly immunogenic in HLA DR3-transgenic mice also had the highest binding affinity to HLA DR3. Identification of T cell determinants restricted to an MHC molecule known to predispose to MG may be an important step toward the development of peptide-based immunomodulation strategies for this autoimmune disease.

Original languageEnglish (US)
Pages (from-to)1118-1124
Number of pages7
JournalJournal of Immunology
Volume167
Issue number2
DOIs
StatePublished - Jul 15 2001

Fingerprint

HLA-DR3 Antigen
Cholinergic Receptors
Transgenic Mice
Myasthenia Gravis
Peptides
T-Lymphocytes
Autoimmune Diseases
Immunomodulation
MHC binding peptide

ASJC Scopus subject areas

  • Immunology

Cite this

Acetylcholine receptor peptide recognition in HLA DR3-transgenic mice : In vivo responses correlate with MHC-peptide binding. / Raju, Raghavan Pillai; Spack, E. G.; David, C. S.

In: Journal of Immunology, Vol. 167, No. 2, 15.07.2001, p. 1118-1124.

Research output: Contribution to journalArticle

@article{be031e2cf8a94164964e0a971c46d417,
title = "Acetylcholine receptor peptide recognition in HLA DR3-transgenic mice: In vivo responses correlate with MHC-peptide binding",
abstract = "HLA DR3 is an MHC molecule that reportedly predisposes humans to myasthenia gravis (MG). Though MG is an Ab-mediated autoimmune disease, CD4+ T cells are essential for the generation of high-affinity Abs; hence the specificities of autoreactive CD4+ T cells are important. In this study we report the HLA DR3-restricted T cell determinants on the extracellular region sequence of human acetylcholine receptor α subunit. We find two promiscuous determinants on this region 141-160 and 171-190 as defined by their immunogenicity in HLA DR3-, HLA DQ8-, and HLA DQ6-transgenic mice in the absence of endogenous mouse class II molecules. We also studied the minimal determinants of these two regions by truncation analysis, and the MHC binding affinity of a set of overlapping peptides spanning the complete sequence region of human acetylcholine receptor α subunit. One of the peptide sequences strongly immunogenic in HLA DR3-transgenic mice also had the highest binding affinity to HLA DR3. Identification of T cell determinants restricted to an MHC molecule known to predispose to MG may be an important step toward the development of peptide-based immunomodulation strategies for this autoimmune disease.",
author = "Raju, {Raghavan Pillai} and Spack, {E. G.} and David, {C. S.}",
year = "2001",
month = "7",
day = "15",
doi = "10.4049/jimmunol.167.2.1118",
language = "English (US)",
volume = "167",
pages = "1118--1124",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Acetylcholine receptor peptide recognition in HLA DR3-transgenic mice

T2 - In vivo responses correlate with MHC-peptide binding

AU - Raju, Raghavan Pillai

AU - Spack, E. G.

AU - David, C. S.

PY - 2001/7/15

Y1 - 2001/7/15

N2 - HLA DR3 is an MHC molecule that reportedly predisposes humans to myasthenia gravis (MG). Though MG is an Ab-mediated autoimmune disease, CD4+ T cells are essential for the generation of high-affinity Abs; hence the specificities of autoreactive CD4+ T cells are important. In this study we report the HLA DR3-restricted T cell determinants on the extracellular region sequence of human acetylcholine receptor α subunit. We find two promiscuous determinants on this region 141-160 and 171-190 as defined by their immunogenicity in HLA DR3-, HLA DQ8-, and HLA DQ6-transgenic mice in the absence of endogenous mouse class II molecules. We also studied the minimal determinants of these two regions by truncation analysis, and the MHC binding affinity of a set of overlapping peptides spanning the complete sequence region of human acetylcholine receptor α subunit. One of the peptide sequences strongly immunogenic in HLA DR3-transgenic mice also had the highest binding affinity to HLA DR3. Identification of T cell determinants restricted to an MHC molecule known to predispose to MG may be an important step toward the development of peptide-based immunomodulation strategies for this autoimmune disease.

AB - HLA DR3 is an MHC molecule that reportedly predisposes humans to myasthenia gravis (MG). Though MG is an Ab-mediated autoimmune disease, CD4+ T cells are essential for the generation of high-affinity Abs; hence the specificities of autoreactive CD4+ T cells are important. In this study we report the HLA DR3-restricted T cell determinants on the extracellular region sequence of human acetylcholine receptor α subunit. We find two promiscuous determinants on this region 141-160 and 171-190 as defined by their immunogenicity in HLA DR3-, HLA DQ8-, and HLA DQ6-transgenic mice in the absence of endogenous mouse class II molecules. We also studied the minimal determinants of these two regions by truncation analysis, and the MHC binding affinity of a set of overlapping peptides spanning the complete sequence region of human acetylcholine receptor α subunit. One of the peptide sequences strongly immunogenic in HLA DR3-transgenic mice also had the highest binding affinity to HLA DR3. Identification of T cell determinants restricted to an MHC molecule known to predispose to MG may be an important step toward the development of peptide-based immunomodulation strategies for this autoimmune disease.

UR - http://www.scopus.com/inward/record.url?scp=0035879206&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035879206&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.167.2.1118

DO - 10.4049/jimmunol.167.2.1118

M3 - Article

C2 - 11441124

AN - SCOPUS:0035879206

VL - 167

SP - 1118

EP - 1124

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -