Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9236718 | Clinical Immunology | 2005 | 13 Pages |
Abstract
The N- and C-terminal flanking domains of the invariant chain peptide, CLIP, have remarkable immunological properties. Addition of these flanking domains to a foreign peptide antigen increases its immunologic potency. The present studies evaluated whether altering a peptide ligand from the tumor-associated antigen c-neu with the flanking domains of CLIP could modify the systemic immune response. The results indicate that the immunogenicity of an MHC class II restricted peptide (NEU) derived from c-neu was significantly altered by addition of the flanking domains from CLIP. Interestingly, selective modification of the peptide with either the N- or the C-terminal flanking domains resulted in functionally divergent systemic immune responses. Immunization of normal F344 rats with the NEU peptide modified with the N-terminal domain of CLIP (N-NEU) resulted in an immune response primarily consisting of type 1 (IL-2, IFNγ) cytokine producing T cells. On the other hand, type 2 (IL-4) cytokine responses were largely predominant following immunization with the self-peptide modified with the C-terminal flanking domain (NEU-C). The functionally divergent responses elicited by the modified self-peptides were accompanied by significant changes in the expression of the CD28/CTLA4/B7 family of co-stimulatory molecules. Immunization with the N-NEU peptide led to enhanced expression of CD28 in the antigen-specific, CD4+ T cell compartment while expression of B7.1 was dramatically reduced in antigen-specific CD8+ T cells. Comparatively, expression of CTLA4 was down-regulated in the antigen-specific CD4+ T cell compartment following immunization with NEU-C peptide. The N-NEU peptide also had a direct effect on dendritic cells leading to the up-regulation of B7.1 expression. Taken together, functionally divergent systemic immune responses can be elicited by strategically altering a self-peptide ligand with the N- and C-terminal flanking domains of CLIP. Moreover, changes in expression of co-stimulatory molecules that are required for T cell activation and T cell-T cell communication may account for the polarization of the immune response elicited by the chimeric peptides.
Keywords
Related Topics
Life Sciences
Immunology and Microbiology
Immunology
Authors
Allan D. Hess, Christopher J. Thoburn, Yuji Miura, Emilie C. Bright,