Tanner M. Johanns

Year Entered: 2004

Degrees Received:
B.A., Biology, University of St. Thomas, 2002

Honors and Awards:
Honors, Year 1, Medical School

Thesis Advisor:  SingSing Way, M.D., Ph.D., MICaB Graduate Program

Thesis Research: 

T cell receptors recognize peptide ligands presented in the context of MHC molecules. However, there appears to be some degeneracy in the peptide:MHC complexes that are recognized by a specific TCR. Furthermore, this degeneracy seems to correlate with the affinity with which a TCR binds to a cognate peptide:MHC complex. In other words, one TCR may recognize several different peptides but with varying affinity.

CD4+ T cells are able to differentiate into several distinct lineages: Th1, Th2, Th17, and Treg. These effector subtypes play important roles in the protective immunity against a wide range of pathogens. Depending on the characteristics of the pathogen, a particular subtype may be more or less important in the clearance of that organism. Therefore, it is crucial that the appropriate CD4+ T cell lineage is generated in response to a specific pathogen in order to ensure that the host will be protected from subsequent encounters.

 Recent evidence has shown that the affinity of the TCR-peptide:MHC binding can influence the differentiation of CD4+ T cells. For example, higher affinity interactions seem to be produce more Th1 cells while lower affinity interactions appear to generate Th2 subsets. Whether this has a role in vivo in the context of infection has yet to be determined.

To test this, we are going to generate attenuated Listeria which express altered peptide ligands of a known immunodominant antigen, Ag85B, found on many Mycobacterium species. These altered peptide ligands will contain mutations in various TCR contact residues which will alter the affinity of the TCR-peptide:MHC interaction. CD4+ T cells from a TCR transgenic mouse that specifically recognizes Ag85B will be adoptively transferred into a naïve congenic recepient mouse. Following infection with an Ag85B variant-expressing Listeria, splenocytes will be collected and the phenotype of the Ag85B-specific CD4+ T cells will be examined. This will allow us to examine the effect of TCR affinity on the resulting immune response.

This work has important implications in vaccine development in the context of selecting which antigen will provide the appropriate immune response following immunization.

Publications: 

Pottorf WJ 2nd, Johanns TM, Derrington SM, Strehler EE, Enyedi A, Thayer SA. Glutamate-induced protease-mediated loss of plasma membrane Ca2+ pump activity in rat hippocampal neurons. J Neurochem. 2006;98:1646-56.

Usachev YM, Marsh AJ, Johann TM, Lemke MM, Thayer SA. "Activation of protein kinase C in sensory neurons accelerates Ca2+ uptake into the endoplasmic reticulum." J Neurosci. 2006;26:311-8.

Goetz CA, Harmon IR, O'Neill JJ, Burchill MA, Johanns TM, Farrar M. Restricted STAT5 activation dictates appropriate thymic B versus T cell lineage commitment. J Immunol. 2005;174:7753-7763.