Peptides containing a dominant T-cell epitope from red cell band 3 have in vivo immunomodulatory properties in NZB mice with autoimmune hemolytic anemia.
The major target of the pathogenic red blood cell (RBC) autoantibodies in New Zealand black (NZB) mice is the anion channel protein band 3, and CD4+ T cells from NZB mice respond to band 3. Here, we demonstrate that a band 3 peptide 861-875, which is the predominant sequence recognized by NZB T cells in vitro, bears a dominant helper epitope able to modulate the autoimmune hemolyic anemia in vivo. The development of RBC-bound autoantibodies and anemia was accelerated in NZB mice injected with peptide 861-874, which is relatively insoluble, and inhalation of the peptide primed T cells for both peptide 861-874 and band 3 responses. By contrast, inhalation of a soluble analog (Glu861, Lys875) of peptide 861-874 deviated the autoimmune response toward a T helper-2 (Th2) profile, with marked increases in the ratio of interleukin-4 to interferon-gamma produced by splenic T cells responding in vitro to either peptide 861-874 or band 3. Moreover, in mice that had received such treatment, the proportion of RBC-bound immunoglobulin G (IgG) molecules that were of the Th2-associated IgG1 isotype was also increased, and anemia was less severe. It is concluded that NZB autoimmune hemolytic anemia is helper dependent and that nasal administration of different peptides containing the dominant T-cell epitope can have potentially detrimental or beneficial effects on the disease.
Shen
Chia-Rui
CR
Department of Pathology and Microbiology, University of Bristol, United Kingdom.
Youssef
Abdel-Rahman
AR
Devine
Anne
A
Bowie
Laura
L
Hall
Andrew M
AM
Wraith
David C
DC
Elson
Christopher J
CJ
Barker
Robert N
RN
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000280:Administration, Inhalation; D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology* / Q000628:therapy; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000276:immunology* / Q000627:therapeutic use; D001323:Autoantibodies / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000627:therapeutic use; D007074:Immunoglobulin G; D051379:Mice; D008814:Mice, Inbred NZB; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D001457:Anion Exchange Protein 1, Erythrocyte; D001323:Autoantibodies; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D010446:Peptide Fragments