CTL recognition of Qa-1b binding a peptide from preproinsulin leader sequences and characterization of Qa-1 from the NOD mouse

Carla J. Aldrich, Taehoon Chun, H Rex Gaskins, Evan Hermel

Research output: Contribution to journalArticle

Abstract

Cytotoxic T lymphocyte (CTL) recognition of major histocompatibility complex (MHC) class I molecules binding peptides is important to the proper functioning of the immune system. Evidence indicates that the MHC class IB molecule Qa-1b, (encoded by H2-T23b) presents antigens to αβ and γδ T cells and that lymphocytes restricted to Qa-1 may play a role in immune regulation. We demonstrate that Qa-1b binds a nonamer peptide derived from the leader sequence of preproinsulin II. Alloreactive anti-Qa-1b CTL lyse Qa-1 plus insulin peptide bearing cells. Blocking assays further demonstrate that this peptide binds in the peptide binding cleft of Qa-1b. DNA sequencing of Qa-1 from the NOD (non obese diabetic, H-2g7) mouse shows that this strain expresses Qa-1a. However, alloreactive CTL recognition of Qa-1 on NOD cells may be unusually influenced by the available peptide pool. In addition, NIT-1, a pancreatic β cell line derived from the NOD mouse is not recognized by anti-Qa-1a CTL, whereas anti-Qa-1b CTL lyse βTC6-F7, a pancreatic line from a normal mouse strain. βTC6 and NIT-1 cells both were killed by anti-H2 class IA CTL. Thus, Qa-1 expression and peptide presentation, particularly on pancreatic β cells may be important in the regulation of autoimmune responses.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

Fingerprint

Inbred NOD Mouse
cytotoxic T-lymphocytes
T-cells
Cytotoxic T-Lymphocytes
Protein Sorting Signals
peptides
Peptides
mice
Major Histocompatibility Complex
major histocompatibility complex
Bearings (structural)
cells
Molecules
autoimmunity
Lymphocytes
Autoimmunity
DNA Sequence Analysis
Immune system
preproinsulin
Immune System

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

CTL recognition of Qa-1b binding a peptide from preproinsulin leader sequences and characterization of Qa-1 from the NOD mouse. / Aldrich, Carla J.; Chun, Taehoon; Gaskins, H Rex; Hermel, Evan.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

@article{52ad7bbdfdf24c8abcaedf4385e199c5,
title = "CTL recognition of Qa-1b binding a peptide from preproinsulin leader sequences and characterization of Qa-1 from the NOD mouse",
abstract = "Cytotoxic T lymphocyte (CTL) recognition of major histocompatibility complex (MHC) class I molecules binding peptides is important to the proper functioning of the immune system. Evidence indicates that the MHC class IB molecule Qa-1b, (encoded by H2-T23b) presents antigens to αβ and γδ T cells and that lymphocytes restricted to Qa-1 may play a role in immune regulation. We demonstrate that Qa-1b binds a nonamer peptide derived from the leader sequence of preproinsulin II. Alloreactive anti-Qa-1b CTL lyse Qa-1 plus insulin peptide bearing cells. Blocking assays further demonstrate that this peptide binds in the peptide binding cleft of Qa-1b. DNA sequencing of Qa-1 from the NOD (non obese diabetic, H-2g7) mouse shows that this strain expresses Qa-1a. However, alloreactive CTL recognition of Qa-1 on NOD cells may be unusually influenced by the available peptide pool. In addition, NIT-1, a pancreatic β cell line derived from the NOD mouse is not recognized by anti-Qa-1a CTL, whereas anti-Qa-1b CTL lyse βTC6-F7, a pancreatic line from a normal mouse strain. βTC6 and NIT-1 cells both were killed by anti-H2 class IA CTL. Thus, Qa-1 expression and peptide presentation, particularly on pancreatic β cells may be important in the regulation of autoimmune responses.",
author = "Aldrich, {Carla J.} and Taehoon Chun and Gaskins, {H Rex} and Evan Hermel",
year = "1998",
month = "3",
day = "20",
language = "English (US)",
volume = "12",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - CTL recognition of Qa-1b binding a peptide from preproinsulin leader sequences and characterization of Qa-1 from the NOD mouse

AU - Aldrich, Carla J.

AU - Chun, Taehoon

AU - Gaskins, H Rex

AU - Hermel, Evan

PY - 1998/3/20

Y1 - 1998/3/20

N2 - Cytotoxic T lymphocyte (CTL) recognition of major histocompatibility complex (MHC) class I molecules binding peptides is important to the proper functioning of the immune system. Evidence indicates that the MHC class IB molecule Qa-1b, (encoded by H2-T23b) presents antigens to αβ and γδ T cells and that lymphocytes restricted to Qa-1 may play a role in immune regulation. We demonstrate that Qa-1b binds a nonamer peptide derived from the leader sequence of preproinsulin II. Alloreactive anti-Qa-1b CTL lyse Qa-1 plus insulin peptide bearing cells. Blocking assays further demonstrate that this peptide binds in the peptide binding cleft of Qa-1b. DNA sequencing of Qa-1 from the NOD (non obese diabetic, H-2g7) mouse shows that this strain expresses Qa-1a. However, alloreactive CTL recognition of Qa-1 on NOD cells may be unusually influenced by the available peptide pool. In addition, NIT-1, a pancreatic β cell line derived from the NOD mouse is not recognized by anti-Qa-1a CTL, whereas anti-Qa-1b CTL lyse βTC6-F7, a pancreatic line from a normal mouse strain. βTC6 and NIT-1 cells both were killed by anti-H2 class IA CTL. Thus, Qa-1 expression and peptide presentation, particularly on pancreatic β cells may be important in the regulation of autoimmune responses.

AB - Cytotoxic T lymphocyte (CTL) recognition of major histocompatibility complex (MHC) class I molecules binding peptides is important to the proper functioning of the immune system. Evidence indicates that the MHC class IB molecule Qa-1b, (encoded by H2-T23b) presents antigens to αβ and γδ T cells and that lymphocytes restricted to Qa-1 may play a role in immune regulation. We demonstrate that Qa-1b binds a nonamer peptide derived from the leader sequence of preproinsulin II. Alloreactive anti-Qa-1b CTL lyse Qa-1 plus insulin peptide bearing cells. Blocking assays further demonstrate that this peptide binds in the peptide binding cleft of Qa-1b. DNA sequencing of Qa-1 from the NOD (non obese diabetic, H-2g7) mouse shows that this strain expresses Qa-1a. However, alloreactive CTL recognition of Qa-1 on NOD cells may be unusually influenced by the available peptide pool. In addition, NIT-1, a pancreatic β cell line derived from the NOD mouse is not recognized by anti-Qa-1a CTL, whereas anti-Qa-1b CTL lyse βTC6-F7, a pancreatic line from a normal mouse strain. βTC6 and NIT-1 cells both were killed by anti-H2 class IA CTL. Thus, Qa-1 expression and peptide presentation, particularly on pancreatic β cells may be important in the regulation of autoimmune responses.

UR - http://www.scopus.com/inward/record.url?scp=33749330541&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749330541&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33749330541

VL - 12

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 5

ER -