1307. Increasing MHC class II diversity in the F1 animal results in profound alterations in the anti-influenza CD4 T cell repertoire when compared to the parental strains
Session: Poster Abstract Session: Viral Immunology and Pathogenesis
Saturday, October 22, 2011
Room: Poster Hall B1
Background: Influenza virus is responsible for annual disease epidemics and occasional pandemics, causing over 300,000 hospitalizations and 40,000 deaths yearly in the United States despite availability of an effective vaccine.  Current vaccination strategy relies upon induction of neutralizing antibody against highly variable surface glycoproteins, necessitating semi-annual vaccine production and yearly vaccine administration to keep pace with antigenic drift.  This has resulted in lower than optimal vaccination rates and an ongoing risk of mismatch between the vaccination and circulating strains.  One way to produce a more broadly protective influenza vaccine would be to utilize cross reactive CD4 T cells to provide focused help to B cells, stimulating accelerated production of high affinity, cross reactive antibodies.  For this strategy to be successful, a better understanding is needed of the factors controlling CD4 T cell immunodominance.  Our past work identified CD4 T cell epitopes restricted to the murine I-Ab and I-As MHC class II molecules.  However humans, unlike inbred strains of mice, may express up to 12 MHC class II molecules simultaneously on the cell surface. 

Methods: To better understand the effect that simultaneous expression of different MHC class II molecules has on CD4 T cell immunodominance, we used EliSpot assay to examine shifts in immunodominance patterns in (C57BL/10 x B10.S)F1 mice (H-2b x s), using previously mapped H-2b and H-2s restricted CD4 T cell epitopes. 

Results: We found a significant decline in the magnitude of response to the majority of epitopes in the F1 strain when compared to the parental strains.  This decline could not be accounted for solely by the lower surface density of MHC class II on the cell or by a failure of APC to stimulate CD4 T cells with lower avidity TCR.   Instead we postulate that our observations may be in part due to alterations in CD4 T cell precursor frequencies due to increased thymic negative selection. 

Conclusion: Given the large diversity and simultaneous allelic usage of MHC class II in humans, these findings have important implications for the rational design of next-generation vaccines.  


Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

Jennifer Nayak, MD, Department of Pediatrics, University of Rochester, Rochester, NY and Andrea Sant, PhD, Department of Microbiology and Immunology, University of Rochester, Rochester, NY

Disclosures:

J. Nayak, None

A. Sant, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.