Unprimed mice harbor a substantial population of "memory-phenotype" CD8 + T cells (CD8-MP cells) that exhibit hallmarks of activation and innate-like functional properties. Due to the lack of faithful markers to distinguish CD8-MP cells from bona fide CD8 + memory T cells, the developmental origins and antigen specificities of CD8-MP cells remain incompletely defined. Using deep T cell antigen receptor (TCR) sequencing, we found that the TCRs expressed by CD8-MP cells are highly recurrent and distinct from the TCRs expressed by naive-phenotype CD8 + T cells. CD8-MP clones exhibited reactivity to widely expressed self-ligands. T cell precursors expressing CD8-MP TCRs upregulated the transcription factor Eomes during maturation in the thymus, prior to induction of the full memory phenotype, suggestive of a unique program triggered by recognition of self-ligands. Moreover, CD8-MP cells infiltrate oncogene-driven prostate tumors and express high densities of PD-1, suggesting a potential role in anti-tumor immunity and response to immunotherapy.

Objective To derive and validate a new ecological measure of the social determinants of health (SDoH), calculable at the zip code or county level. Data Sources and Study Setting The most recent releases of secondary, publicly available data were collected from national U.S. health agencies as well as state and city public health departments. Study Design The Social Vulnerability Metric (SVM) was constructed from U.S. zip‐code level measures (2018) from survey data using multidimensional Item Response Theory and validated using outcomes including all‐cause mortality (2016), COVID‐19 vaccination (2021), and emergency department visits for asthma (2018). The SVM was also compared with the existing Centers for Disease Control and Prevention's Social Vulnerability Index (SVI) to determine convergent validity and differential predictive validity. Data Collection/Extraction Methods The data were collected directly from published files available to the public online from national U.S. health agencies as well as state and city public health departments. Principal Findings The correlation between SVM scores and national age‐adjusted county all‐cause mortality was r = 0.68. This correlation demonstrated the SVM's robust validity and outperformed the SVI with an almost four‐fold increase in explained variance (46% vs. 12%). The SVM was also highly correlated (r ≥ 0.60) to zip‐code level health outcomes for the state of California and city of Chicago. Conclusions The SVM offers a measurement tool improving upon the performance of existing SDoH composite measures and has broad applicability to public health that may help in directing future policies and interventions. The SVM provides a single measure of SDoH that better quantifies associations with health outcomes.

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IMPORTANCE There has been large geographic inequity in vaccination coverage across Chicago, Illinois, with higher vaccination rates in zip codes with residents who predominantly have high incomes and are White. OBJECTIVE To determine the association between inequitable zip code-level vaccination coverageand COVID-19 mortality in Chicago.

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