Two unusual minor histocompatibility models in mice

描述(由申请者提供)：这些调查承诺通过为学生提供各种明确的项目来加强CCSU的研究活动，这些项目侧重于进一步表征小鼠中两种不寻常的次要组织相容性(H)模型：H-Hix和H.mshi。 H-HIX。X染色体上的组织不亲和性。对X连锁微小移植障碍的经典分析表明，一个单一的多态基因(Hxa)导致了不同近交系小鼠之间的皮肤移植不相容。我们最近对先前描述的C57BL/6和BALB/c株的X连锁不亲和性进行的进一步研究表明，这种同种异体移植排斥反应是由至少两个不同的抗原介导的，这些抗原可能是多个基因的产物。因此，我们认为这两个菌株编码不同单倍型的抗原编码基因(称为H-hixb和H-hixC)，而不是单个HxA基因座的不同等位基因。此外，我们假设其他菌株组合可能识别额外的、不同的X连锁抗原编码基因座。在这里，我们建议对H-hixb、H-hixc差异以及我们旨在识别的其他H-Hix单倍型对进行遗传作图，以检验目前关于次要组织相容性基因座结构的两种模型，并为未来克隆和分子分析每个不同的H-Hix组分提供基础。 H-Mshi用于与Mshi突变相关的组织不相容。男性不育和组织不相容突变(Mshi)最初是在BALB/c的遗传背景上检测到的，是一种自发的抗原缺失型H变异体，排斥野生型皮肤移植。我们之前对该变体的研究表明，H-mshi可能是一种新型的次要组织相容性基因，该基因是由单个高度保守的基因突变引起的；并介导了一种不寻常的细胞毒性T淋巴细胞非依赖性排斥机制。此外，我们已经将mshi基因定位到一个包含不到20个基因的小区域。在这里，我们建议对这些候选基因进行筛选，以确定被mshi突变破坏的基因。为了确认H-mshi的分子归属，并对H-mshi的功能和结构进行完整的剖析，我们还建议分离一个T辅助细胞克隆和对H-mshi+抗原具有特异性反应的血清抗体。

DESCRIPTION (provided by applicant): These investigations promise to enhance research activity at CCSU by providing students with a variety of defined projects focused on the further characterization of two unusual minor histocompatibility (H) models in mice: H-hix and H.mshi. H-hix. for histoincompatibilitv on the X chromosome. Classical analysis of X-linked minor transplantation barriers has suggested that a single, polymorphic gene (Hxa) is responsible for generating skin-graft incompatibility among different inbred strains of mice. Our recent efforts to further characterize the X-linked incompatibility previously described for strains C57BL/6 and BALB/c has shown instead that this allograft rejection is mediated by at least two distinct antigens that are likely the products of more than one gene. Thus, we propose that these two strains encode different haplotypes of antigen-encoding loci (called H-hixb and H-hixC), rather than different alleles of a single Hxa locus. Furthermore, we hypothesize that other strain combinations may identity additional, distinct sets of X-linked antigen-encoding loci. Here we propose to genetically map the H-hixb, H-hixc disparity--as well as other H-hix haplotype pairs that we aim to identity--to test two current models regarding minor histocompatibility locus structure, and to provide a foundation for the future cloning and molecular analysis of each distinct H-hix component. H-mshi for histoincompatibility associated with the mshi mutation. The male sterility and histoincompatibility mutation (mshi) was initially detected on a BALB/c genetic background as a spontaneous antigen-loss type H variant that rejected wild-type skin grafts. Our previous work with this variant has shown that H-mshi may exemplify a new type of minor histocompatibility locus that has resulted from the mutation of a single, highly conserved gene; and mediates an unusual, cytotoxic-T-lymphocyte-independent rejection mechanism. In addition, we have genetically mapped mshi to a small region that includes fewer than 20 genes. Here we propose to screen these candidates to identify the gene disrupted by the mshi mutation. To confirm this molecular assignment and to allow the complete functional and structural dissection of H-mshi, we also propose to isolate a T-helper cell clone and serum antibodies specifically reactive to the H-mshi+ antigens.