Creating and use of an new experimental preclinical HLA transgenic mice model to mapping HLA-restricted T cells epitopes for polyepitopes vaccine design.

• Main Author: Ru, Zhitao
• Language: ENG
• Published: Université Paris Sud - Paris XI 2012
• Subjects: [SDV:SA] Life Sciences/Agricultural sciences; HLA-A2/DP4; Epitopes; Humanized mice
• Online Access: http://tel.archives-ouvertes.fr/tel-00714984; http://tel.archives-ouvertes.fr/docs/00/71/49/84/PDF/VA_RU_Zhitao_21022012.pdf

A new homozygous humanized HLA transgenic mouse strain, HLA-A2.1+/+HLA-DP4+/+hCD4+/+mCD4-/-IAβ-/-β2m-/- (HLA-A2/DP4), was obtained by crossing the HLA transgenic HLA-A2.1+/+β2m-/-(A2) mice and HLA transgenic HLA-DP4+/+hCD4+/+mCD4-/-IAβ-/-(DP4) mice. In HLA-A2/DP4 mice, HLA-A2 restricted or HLA-DP4 restricted T cell responses against HBs antigen of hepatitis B virus after immunization with the HBsAg vaccine are similar to those induced in A2 mice, in DP4 mice, in HBV-infected or HBsAg-vaccinated humans. These results show that cellular responses induced in HLA-A2/DP4 mice faithfully mimic human responses counterparts. Thus, these mice represent an excellent animal model for preclinical experimentations to evaluate or compare the effectiveness of responses "human" induced in vivo by candidate vaccines. The model will also facilitate the identification of new epitopes HLA-A2 and HLA-DP4 restricted, which will be of future reactive for clinical monitoring response against infection in humans. By exploiting these HLA-A2/DP4 mice, we identified four new HLA-DP4-restricted epitopes from HBsAg and two new HLA-A2 restricted epitopes derived from protein M1.