Transgenic Mice and Mutants in MHC Research

This volume contains papers presented at the international conference on "Transgenic Mice and Mutants in MHC Research", held in Bar Harbor, Maine, in June, 1989. The meeting brought together eighty researchers working in the field. While mouse H-2 mutants have been known for many years their studies continue to contribute a great deal to our understanding of structure/function relationships and evolution of MHC molecules. Recently a new direction of research has emerged on regulation, expression and function of MHC genes using transgenic animals carrying exogenous MHC genes from the same or other species or engineered MHC genes. With the introduction of transgenic mice more specific questions about the various functions of MHC genes can be answered as, for example, the role of soluble and membrane-bound MHC molecules in self tolerance and elimination of specific T cell clones, recognition of human MHC antigens by the mouse immune system, the role of individual human MHC genes in disease susceptibility. New approaches for evaluation of the role of MHC linked and unlinked genes in susceptibility of mice to malignant tumors and their metastases have been also reported. Our purpose has been to provide a forum for discussion of these new developments. Many questions remain to be answered but the necessary tools have become available. We thank the contributors and hope that the readers will benefit from this Pro­ ceedings. We wish to acknowledge the financial sponsorship for the meeting by The Pew Charitable Trust and Howard Hughes Medical Institute.

Table of Contents:
I. Mutant Models of MHC Antigen Expression and Function (H-2).- Spontaneous Frequency of H-2 Mutations.- Microgene Conversion in the Evolution of the MHC Class I Multigene Family.- Random Mutagenesis by Oligonucleotides: A Probe for MHC Structure and Function.- Altered Recognition of LCMV Antigen Presented on Mutant Class I Molecules.- Relationship Between Class II Structure and B Cell Signaling.- Multivalent Requirement for the Stimulation of Alloreactive T Cells: Studies with Engineered Soluble MHC Class I Proteins In Vitro and In Vivo.- Novel MHC Variants Spliced by Overlap Extension.- The Functional Significance of Amino Acid Polymorphisms in Class I MHC Molecules.- Products of Separate Genes Encoded Within Minor Histocompatibility Loci Stimulate Class I and Class II MHC-Restricted T Cells.- Determination of Distinction Odortypes by Mutation of Class I and Class II MHC Genes.- II. Mutants of MHC Genes as Probes of Immunological Function (HLA).- Analysis of HLA-B27-Specific T-Cell Epitopes with Site-Directed Mutants Mimicking HLA-B27 Polymorphism.- The Role of Amino Acid Position and Side Chain Structure in Serological and CTL-Defined Epitopes on the HLA-A2.1 Molecule.- Two Amino Acids on the ? Helical Region of the ?1 Domain Form Multiple Epitopes Recognized by HLA-Bw52 Specific Human Cytotoxic T Cell.- III. Regulation of MHC Gene Expression.- Mouse Mammary Tumor Virus-Directed Gene Expression in Transgenic Mice.- Regulation of Class I MHC Expression: In Vivo Function of Regulatory DNA Sequence Elements in Transgenic Mice.- Expression of a Non-Classical Class I Gene in Transgenic Mice.- Regulation of Expression of Human MHC Class I Heavy (HLA-B7) and Light (h?2-m) Chain Genes in Transgenic Mice.- Cloned Trans-Acting Factors that Bind to the Regulatory Elements ofthe Major Histocompatibility Complex Class I Gene.- Transcriptional Regulation of MHC Class II Gene Expression: Are MHC Class II Genes Coordinately Regulated?.- The Effect of Copy Number on mRNA and Cell Surface Expression of an A?k Transgene.- Construction of Retroviral Vectors for the Study of Tissue-Specific Regulation of Human MHC Class II Genes.- IV. Expression and Function of Class I Genes in Transgenic Mice.- Male Sterility in HLA-B27-Transgenic Mice.- The Lyt-2 Accessory Molecule is Responsible for the Weak Mouse Anti-HLA Xeno-Response.- Human HLA-B27 Antigen in Transgenic Mice can Function as a Major Histocompatibility Antigen.- Cytotoxic T Cell Responses Against Human Class I Molecules in Normal and HLA-A2.1 Transgenic Mice.- Analysis of the HLA-Cw3 Specific CTL Response of HLA-B7x Human ?2 Microglobulin Transgenic Mice.- H-2-Restricted Recognition of Xeno-MHC Antigens by Primary Mouse Cytotoxic T Cells is the Exception Rather than the Rule.- Copy Number and the Presence of Human ?2-Microglobulin Control Cell Surface Expression of HLA-B27 Antigen in Transgenic Mice with a 25 kb B27 Gene Fragment.- Expression and Function in a Transgenic Mouse of an H-2Kb Variant Gene Obtained by Site-Directed Mutagenesis in a Kbm1 Mutant Mouse.- V. Expression and Function of Class II Genes in Transgenic Mice.- Clonal Anergy in Transgenic Mice with Pancreatic Expression of MHC Class II I-E.- Role of Ia Antigens in Clonal Deletion of T Cells: Studies with Recombinant and Transgenic Mice.- Transgenic Mice with MHC Class II Genes: The Use in the Study of Allelic ?/? Chain Pairing and the Production of Engineered Mice with Mutant I-A Genes.- T Cell Recognition of Major Histocompatibility Complex Antigens in HLA Class II Transgenic Mice.- VI. Transgenic and Mutant Models ofDisease.- HLA-B27 and Arthritis.- HLA-B27 Transgenic Mice as Potential Models of Human Disease.- Mouse Mutants Affecting Growth and Metastasis of a Syngeneic Tumor.- Transgene Induced MHC Mismatch Results in Rapid Natural Killer Cell Dependent Elimination of Lymphoma Cells.- Highly Immunogenic Transformed Tumor Clones Expressing Allogeneic Class I Histocompatibility Gene Demonstrate a Specific Immunotherapeutic Affect Against the Parental Tumor.- Graft Specific MHC Class II Gene Expression During Allograft Response.- Influence of MHC and Non-MHC Genes on Tumorigenesis and the Use of the Recombinant Congenic Strains as a Novel Tool for the Genetic Analysis of Tumor Susceptibility.