CLASS IB GENES IN RESPONSE TO INFECTIONS

IA类分子在细胞内寄生虫向CD8T细胞递送多肽表位的过程中起主要作用。IB类分子不像IA类分子那样多态，其功能也不太清楚。我们计划利用其IA类(KbDb)基因缺失的H-2b小鼠。与之前描述的I类缺陷动物(β-2M-/-和Tap-1-/-)不同，这些小鼠完全缺乏IA类分子，但保留了IB类的表达。将测试它们对3种细胞内病原体的反应能力，即单核细胞增生性李斯特氏菌、牛痘病毒和水泡性口炎病毒。已知CD8细胞在抵抗这些病原体方面发挥作用，在LM的情况下，已知可以在体外产生由2个IB类分子M3和Qa-1b呈现的CTL。IB类分子在这些感染中提供免疫的作用将通过评估体内各种T细胞亚群和NK细胞的作用来分析。我们还将在体外分析这些反应，并确定IB类分子呈递给抗原特异性CD8细胞的表位。最后，由于KB-/-DB-/-小鼠不能在IA类分子上产生CD8谱系，我们将确定这些动物是否有针对自身H-2b类IA分子以及其他IA类同种异体抗原的谱系。

Class IA molecules play a major role in the presentation of peptide epitopes from intracellular parasites to CD8 T cells. Class IB molecules are not as polymorphic as class IA and their function is less well understood. We plan to utilize H-2b mice that have their class IA (KbDb) genes deleted. Unlike previously described class I deficient animals (beta-2M-/- and Tap-1-/-) these mice have a complete absence of class IA molecules but retain class IB expression. They will be tested for their ability to respond to 3 intracellular pathogens, Listeria monocytogenes (LM), vaccinia virus, and vesicular stomatitis virus. CD8 cells are known to play a role in resistance to these pathogens and in the case of LM, it is known that CTL can be generated in vitro against this pathogen presented by 2 class IB molecules, M3 and Qa-1b. The role that class IB molecules play in these infections in providing immunity will be analyzed by assessing the role of various T cell subsets as well as NK cells in vivo. We will also analyze these responses in vitro and identify the epitopes presented by class IB molecules to antigen specific CD8 cells. Finally, since Kb-/-Db-/- mice cannot generate their CD8 repertoire on class IA molecules, we will determine whether these animals have a repertoire directed against both self H-2b class IA molecules as well as other class IA alloantigens.