Walser-Kuntz, Debby

Abstract The rapidly changing nature of immunology makes it a challenging course for both undergraduate students and faculty. A teaching approach that incorporates essential immunological techniques and an introduction to the primary literature helps undergraduates navigate the discipline and remain current. Case studies are an effective active learning approach that provide real world examples to engage undergraduates and an opportunity for hands on problem solving, data analysis, and critical thinking as students must consider outcomes and consequences. Although case studies that explore clinical connections already exist for undergraduates, they do not include key techniques or provide experience working with the primary literature. We have developed several case studies to help undergraduate immunology students understand and analyze data involving: flow cytometry, CRISPR/Cas, CAR T cells, and ELISAs. The case studies 1) introduce students to techniques and methods they may not have access to in their laboratory courses due to the lack of appropriate instruments or the cost of reagents, 2) build on difficult concepts covered in the course, and 3) incorporate figures from papers that challenge students to apply what they have learned. Assessment of student learning includes in-class quizzes and small group responses to data analysis questions, the use of "clickers"/personal response system, and related exam questions. Students self-report that the case studies are a highly effective teaching method that allow them to both reinforce their understanding of the course material and apply it to practical problems.

Abstract We have identified in an extracellular segment of the alpha1 subunit of nicotinic acetylcholine receptor (AChR) of homologous muscle a 17-residue autoantigen that, without conjugation to a carrier, activates Th lymphocytes and induces production of autoantibodies that cause electrophysiologic signs of experimental autoimmune myasthenia gravis. A panel of overlapping synthetic peptides revealed two T cell epitopes, one encompassed by residues 121-136 and the other by 129-145. Residues 129 (glutamic acid) and 130 (isoleucine) were implicated in a pathogenic B cell epitope. Peptide 129-145 (Glu-Ile-Ile-Val-Thr-His-Phe-Pro-Phe-Asp-Glu-Gln-Asn-Cys-Ser-Met-Lys, a conserved sequence in rat and human AChR) induced autoantibody production in 76% of rats. All seropositive rats had evidence of experimental autoimmune myasthenia gravis; five of five tested had electrophysiologic signs, and all had loss of immunochemically measured autologous muscle AChR. Analogues of 129-145, with single residues substituted by alanine, revealed phenylalanine 135, phenylalanine 137, and glutamic acid 139 as most important determinants of Ag/MHC-II/TCR interactions; phenylalanine 137 is critical for T cell activation. B cells were the major MHC-II-positive cell type to which the self-peptide 129-145 bound in a population of nonimmune splenic cells. More efficient processing and presentation of the Th cell epitope by an expanded population of immune B cells selected by specifically binding another epitope of the same peptide would greatly amplify the production of autoantibodies. Peptide autoantigens of this type could plausibly perpetuate the autoantibody response in myasthenia gravis, and are a rational target for strategies aimed at Ag-specific therapeutic intervention.