Inhibition of T cell responses by transferrin-coupled competitor peptides.
Activation of helperT cell has been implicated in a number of autoimmune diseases including rheumatoid arthritis. The underlying mechanism that initiates and promotes disease progression remains unclear, but it is apparent that helper T cells and autoantigens play prominent roles. Identification of the autoantigens has proven to be extremely difficult, and therefore strategies for promoting tolerance induction remain limited. Since autoimmune diseases are closely associated with specific major histocompatibility complex class II molecules such as HLA-DR4, the use of competitor peptides is an alternative strategy. A limitation of competitor peptides, however, is that they are ineffective in vivo. In the studies presented here, we demonstrate that coupling competitor peptides to a cell-surface receptor ligand, transferrin, enhances their ability to block helper T cell responses using the DO11.10 transgenic mouse as our model system.
Zaliauskiene
Lolita
L
Department of Cell Biology and the UAB Comprehensive Cancer Center, University of Alabama at Birmingham, 35294-0005, USA.
Fazio
Rebecca L
RL
Kang
Sunghyun
S
Sparks
Kerri
K
Weaver
Casey T
CT
Zinn
Kurt R
KR
Collawn
James F
JF
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D001324:Autoantigens / Q000378:metabolism; D001667:Binding, Competitive; D003432:Cross-Linking Reagents; D004705:Endocytosis; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D014168:Transferrin / Q000378:metabolism / Q000494:pharmacology*
D001324:Autoantigens; D003432:Cross-Linking Reagents; D018796:Immunoconjugates; D010455:Peptides; D014168:Transferrin