David A. Hafler

Automated high-dimensional flow cytometric data analysis (2009)

Pyne, Saumyadipta, Hu, Xinli, Wang, Kui, Rossin, Elizabeth, Lin, Tsung-I., Maier, Lisa M., ...

Flow cytometric analysis allows rapid single cell interrogation of surface and intracellular determinants by measuring fluorescence intensity of fluorophore-conjugated reagents. The availability of...

Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS (2009)

Kallio, Suvi P., Jakkula, Eveliina, Purcell, Shaun, Suvela, Minna, Koivisto, Keijo, Tienari, Pentti J., ...

Large case–control genome-wide association studies primarily expose common variants contributing to disease pathogenesis with modest effects. Thus, alternative strategies are needed to tackle rare,...

The role of the CD58 locus in multiple sclerosis (2009)

Baecher-Allan, Clare, Maier, Lisa M, Arthur, Ariel T, Ottoboni, Linda, Barcellos, Lisa, ...

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with demyelination and axonal loss. A whole genome association scan suggested that allelic variants in the...

A second major histocompatibility complex susceptibility locus for multiple sclerosis (2007)

Gregory, Simon G, Barcellos, Lisa F, Walton, Amie, ...

Objective: Variation in the major histocompatibility complex (MHC) on chromosome 6p21 is known to influence susceptibility to multiple sclerosis with the strongest effect originating from the...

A High-Density Admixture Map for Disease Gene Discovery in African Americans (2004)

Smith, Michael W, Patterson, Nick, Lautenberger, James A, Truelove, Ann L, McDonald, Gavin J, Waliszewska, Alicja, ...

Admixture mapping (also known as “mapping by admixture linkage disequilibrium,” or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans,...

Enhancing linkage analysis of complex disorders: An evaluation of high-density genotyping (2004)

Sawcer, Stephen J, Maranian, Mel, Singlehurst, Sarah, Yeo, TaiWai, Compston, Alastair, ...

To explore the potential value of recently developed high density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK...

Enhancing linkage analysis of complex disorders: An evaluation of high-density genotyping (2004)

Sawcer, Stephen J, Maranian, Mel, Singlehurst, Sarah, Yeo, TaiWai, Compston, Alastair, ...

To explore the potential value of recently developed high density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK...

HST.176 Cellular and Molecular Immunology, Fall 2002 (2002)

Pillai, Shiv, Anderson, Paul, Auchincloss, Hugh, Balk, Steven, Cherayil, Bobby, Davis, Benjamin, ...

Covers cells and tissues of the immune system, lymphocyte development, the structure and function of antigen receptors, the cell biology of antigen processing and presentation including molecular...

HST.176 Cellular and Molecular Immunology, Fall 2002 (2002)

Pillai, Shiv, Anderson, Paul, Auchincloss, Hugh, Balk, Steven, Cherayil, Bobby, Davis, Benjamin, ...

Covers cells and tissues of the immune system, lymphocyte development, the structure and function of antigen receptors, the cell biology of antigen processing and presentation including molecular...

Multiple differences in gene expression in regulatory Vα24JαQ T cells from identical twins discordant for type I diabetes

Wilson, S. Brian, Kent, Sally C., Horton, Heidi F., Hill, Andrew A., Bollyky, Paul L., Hafler, David A., ...

Quantitative and qualitative defects in CD1d-restricted T cells have been demonstrated in human and murine autoimmune diseases. To investigate the transcriptional consequences of T cell receptor...

Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers

Meyer, Abbie L., Trollmo, Christina, Crawford, Frances, Marrack, Philippa, Steere, Allen C., Huber, Brigitte T., ...

We characterized antigen-specific CD4+ T cells in six patients with treatment-resistant Lyme arthritis, using an HLA-DRB1*0401 major histocompatibility complex (MHC) class II tetramer covalently...

Heterophile antibodies segregate in families and are associated with protection from type 1 diabetes

She, Jin-Xiong, Ellis, Tamir M., Wilson, S. Brian, Wasserfall, Clive H., Marron, Michele, Reimsneider, Sharon, ...

Markedly elevated levels of serum IL-4 were reported previously in 50% of a small group of type 1 diabetes nonprogessors. To determine the patterns of expression for this phenotype, a larger cohort...

GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes

Viglietta, Vissia, Kent, Sally C., Orban, Tihamer, Hafler, David A.

Insulin-dependent type 1 diabetes is an autoimmune disease mediated by T lymphocytes recognizing pancreatic islet cell antigens. Glutamic acid decarboxylase 65 (GAD65) appears to be an important...

Multiple sclerosis

Hafler, David A.

Multiple sclerosis is a complex genetic disease associated with inflammation in the CNS white matter thought to be mediated by autoreactive T cells. Clonal expansion of B cells, their antibody...

Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis

Duda, Petra W., Schmied, Mascha C., Cook, Sandra L., Krieger, Jeffrey I., Hafler, David A.

We examined the effect of glatiramer acetate, a random copolymer of alanine, lysine, glutamic acid, and tyrosine, on antigen-specific T-cell responses in patients with multiple sclerosis (MS)....

Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis

Astier, Anne L., Meiffren, Gregory, Freeman, Samuel, Hafler, David A.

Loss of Treg function appears to be a critical factor in the pathogenesis of human autoimmune diseases. Attention has focused on defects of CD4+CD25high Tregs, and techniques have been developed to...

Multiple differences in gene expression in regulatory Vα24JαQ T cells from identical twins discordant for type I diabetes

Wilson, S. Brian, Kent, Sally C., Horton, Heidi F., Hill, Andrew A., Bollyky, Paul L., Hafler, David A., ...

Quantitative and qualitative defects in CD1d-restricted T cells have been demonstrated in human and murine autoimmune diseases. To investigate the transcriptional consequences of T cell receptor...

Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers

Meyer, Abbie L., Trollmo, Christina, Crawford, Frances, Marrack, Philippa, Steere, Allen C., Huber, Brigitte T., ...

We characterized antigen-specific CD4+ T cells in six patients with treatment-resistant Lyme arthritis, using an HLA-DRB1*0401 major histocompatibility complex (MHC) class II tetramer covalently...

Heterophile antibodies segregate in families and are associated with protection from type 1 diabetes

She, Jin-Xiong, Ellis, Tamir M., Wilson, S. Brian, Wasserfall, Clive H., Marron, Michele, Reimsneider, Sharon, ...

Markedly elevated levels of serum IL-4 were reported previously in 50% of a small group of type 1 diabetes nonprogessors. To determine the patterns of expression for this phenotype, a larger cohort...

GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes

Viglietta, Vissia, Kent, Sally C., Orban, Tihamer, Hafler, David A.

Insulin-dependent type 1 diabetes is an autoimmune disease mediated by T lymphocytes recognizing pancreatic islet cell antigens. Glutamic acid decarboxylase 65 (GAD65) appears to be an important...

Multiple sclerosis

Hafler, David A.

Multiple sclerosis is a complex genetic disease associated with inflammation in the CNS white matter thought to be mediated by autoreactive T cells. Clonal expansion of B cells, their antibody...

Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis

Duda, Petra W., Schmied, Mascha C., Cook, Sandra L., Krieger, Jeffrey I., Hafler, David A.

We examined the effect of glatiramer acetate, a random copolymer of alanine, lysine, glutamic acid, and tyrosine, on antigen-specific T-cell responses in patients with multiple sclerosis (MS)....

A High-Density Admixture Map for Disease Gene Discovery in African Americans

Smith, Michael W., Patterson, Nick, Lautenberger, James A., Truelove, Ann L., McDonald, Gavin J., Waliszewska, Alicja, ...

Admixture mapping (also known as “mapping by admixture linkage disequilibrium,” or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans,...

Methods for High-Density Admixture Mapping of Disease Genes

Patterson, Nick, Hattangadi, Neil, Lane, Barton, Lohmueller, Kirk E., Hafler, David A., Oksenberg, Jorge R., ...

Admixture mapping (also known as “mapping by admixture linkage disequilibrium,” or MALD) has been proposed as an efficient approach to localizing disease-causing variants that differ in frequency...

Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis

Astier, Anne L., Meiffren, Gregory, Freeman, Samuel, Hafler, David A.

Loss of Treg function appears to be a critical factor in the pathogenesis of human autoimmune diseases. Attention has focused on defects of CD4+CD25high Tregs, and techniques have been developed to...

Dysregulated T cell expression of TIM3 in multiple sclerosis

Koguchi, Ken, Anderson, David E., Yang, Li, O'Connor, Kevin C., Kuchroo, Vijay K., Hafler, David A.

T cell immunoglobulin- and mucin domain–containing molecule (TIM)3 is a T helper cell (Th)1–associated cell surface molecule that regulates Th1 responses and promotes tolerance in mice, but its...

Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis

Viglietta, Vissia, Baecher-Allan, Clare, Weiner, Howard L., Hafler, David A.

CD4+CD25+ regulatory T cells contribute to the maintenance of peripheral tolerance by active suppression because their deletion causes spontaneous autoimmune diseases in mice. Human CD4+ regulatory T...

Suppressor T Cells in Human Diseases

Baecher-Allan, Clare, Hafler, David A.

Although central and peripheral tolerance are important for the regulation of human immune responses to self- and microbial antigens, an important role of suppressor CD4+ CD25+ T cells is suggested...

Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function

Lim, Dong-Gyun, Slavik, Jacqueline M., Bourcier, Katarzyna, Smith, Kathrine J., Hafler, David A.

T cell receptors recognize small changes in peptide ligands leading to different T cell responses. Here, we analyzed a panel of HLA-A2–Tax11-19 reactive T cell clones to examine how small allelic...

Direct Ex Vivo Analysis of Activated, Fas-sensitive Autoreactive T Cells in Human Autoimmune Disease

Bieganowska, Katarzyna D., Ausubel, Lara J., Modabber, Yalda, Slovik, Elissa, Messersmith, Wells, Hafler, David A.

The frequency of clonally expanded and persistent T cells recognizing the immunodominant autoantigenic peptide of myelin basic protein (MBP)p85-99 was directly measured ex vivo in subjects with...

Allelic variant in CTLA4 alters T cell phosphorylation patterns

Maier, Lisa M., Anderson, David E., De Jager, Philip L., Wicker, Linda S., Hafler, David A.

Little is known regarding the functional effects of common autoimmune susceptibility variants on human immune cells. The SNP CT60 (rs3087243; A/G) located in the 3′ UTR of the CTLA4 gene has been...

IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production

Maier, Lisa M., Lowe, Christopher E., Cooper, Jason, Downes, Kate, Anderson, David E., Severson, Christopher, ...

Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte...

TIMs: central regulators of immune responses

Hafler, David A., Kuchroo, Vijay

Exhaustion of T cell responses during chronic viral infections has been observed in both mouse and man and has been attributed to up-regulation of PD-1 on the surface of exhausted T cells. In...

Automated high-dimensional flow cytometric data analysis

Pyne, Saumyadipta, Hu, Xinli, Wang, Kui, Rossin, Elizabeth, Lin, Tsung-I, Maier, Lisa M., ...

Flow cytometric analysis allows rapid single cell interrogation of surface and intracellular determinants by measuring fluorescence intensity of fluorophore-conjugated reagents. The availability of...

The role of the CD58 locus in multiple sclerosis

De Jager, Philip L., Baecher-Allan, Clare, Maier, Lisa M., Arthur, Ariel T., Ottoboni, Linda, Barcellos, Lisa, ...

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with demyelination and axonal loss. A whole genome association scan suggested that allelic variants in the...