Tissue-Specific Expression of Self Peptides Bound by Major Histocompatibility Complex Class II Molecules

2015 ◽  
pp. 88-112
Author(s):  
John H. Freed ◽  
Philippa Marrack
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Histocompatibility Complex ◽  
Self Peptides

Identification of cis sequences controlling efficient position-independent tissue-specific expression of human major histocompatibility complex class I genes in transgenic mice

1991 ◽  
Vol 11 (7) ◽  
pp. 3564-3572 ◽  
Author(s):  
J W Chamberlain ◽  
H A Vasavada ◽  
S Ganguly ◽  
S M Weissman
Keyword(s):  
Major Histocompatibility Complex ◽  
Transgenic Mice ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Specific Expression ◽  
Tissue Specific ◽  
Cis Acting ◽  
Tissue Specific Expression ◽  
Histocompatibility Complex

We previously reported that genomic major histocompatibility complex class I human leukocyte antigen (HLA)-B7 gene constructs with as little as 0.66 kb of 5'- and 2.0 kb of 3'-flanking DNA were expressed efficiently and appropriately in transgenic mice. To identify and characterize the relevant cis-acting regulatory elements in more detail, we have generated and analyzed a series of transgenic mice carrying native HLA-B7 genes with further 5' truncations or intronic deletions and hybrid constructs linking the 5'-flanking region of B7 to a reporter gene. We were unable to detect a specific requirement for sequence information within introns 2 to 7 for either appropriate constitutive or inducible class I expression in adult animals. The results revealed the presence of cis-acting regulatory sequences between -0.075 kb and -0.66 kb involved in driving efficient copy number-dependent constitutive and gamma interferon-enhanced tissue-specific expression. The region from -0.11 to -0.66 kb is also sufficient to prevent integration site-specific "position effects," because in its absence HLA-B7 expression is frequently detected at significant levels at inappropriate sites. Conserved sequence elements homologous to the H-2 class I regulatory element, or enhancer A, and the interferon response sequence are located between about -151 and -228 bp of the B7 gene. Our results also indicate the existence of sequences downstream of -0.11 kb which can influence the pattern of tissue-specific expression of the HLA-B7 gene and the ability of this gene to respond to gamma interferon.

scholarly journals Invariant Chain–independent Function of H-2M in the Formation of Endogenous Peptide–Major Histocompatibility Complex Class II Complexes In Vivo

1998 ◽  
Vol 187 (2) ◽  
pp. 245-251 ◽  
Author(s):  
Susan Kovats ◽  
Catherine E. Grubin ◽  
Susan Eastman ◽  
Paul deRoos ◽  
Ashok Dongre ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Invariant Chain ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Self Peptides

Efficient loading of major histocompatibility complex class II molecules with peptides requires the invariant chain (Ii) and the class II–like molecule H-2M. Recent in vitro biochemical studies suggest that H2-M may function as a chaperone to rescue empty class II dimers. To test this hypothesis in vivo, we generated mice lacking both Ii and H-2M (Ii−/−M−/−). Antigen presenting cells (APCs) from Ii−/−M−/− mice, as compared with APCs from Ii−/− mice, exhibit a significant reduction in their ability to present self-peptides to a panel of class II I-Ab–restricted T cells. As a consequence of this defect in the loading of self peptides, CD4+ thymocyte development is profoundly impaired in Ii−/−M−/− mice, resulting in a peripheral CD4+ T cell population with low levels of T cell receptor expression. These findings are consistent with the idea that H-2M functions as a chaperone in the peptide loading of class II molecules in vivo.

scholarly journals Identification of cis sequences controlling efficient position-independent tissue-specific expression of human major histocompatibility complex class I genes in transgenic mice.

1991 ◽  
Vol 11 (7) ◽  
pp. 3564-3572 ◽  
Author(s):  
J W Chamberlain ◽  
H A Vasavada ◽  
S Ganguly ◽  
S M Weissman
Keyword(s):  
Major Histocompatibility Complex ◽  
Transgenic Mice ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Specific Expression ◽  
Tissue Specific ◽  
Cis Acting ◽  
Tissue Specific Expression ◽  
Histocompatibility Complex

We previously reported that genomic major histocompatibility complex class I human leukocyte antigen (HLA)-B7 gene constructs with as little as 0.66 kb of 5'- and 2.0 kb of 3'-flanking DNA were expressed efficiently and appropriately in transgenic mice. To identify and characterize the relevant cis-acting regulatory elements in more detail, we have generated and analyzed a series of transgenic mice carrying native HLA-B7 genes with further 5' truncations or intronic deletions and hybrid constructs linking the 5'-flanking region of B7 to a reporter gene. We were unable to detect a specific requirement for sequence information within introns 2 to 7 for either appropriate constitutive or inducible class I expression in adult animals. The results revealed the presence of cis-acting regulatory sequences between -0.075 kb and -0.66 kb involved in driving efficient copy number-dependent constitutive and gamma interferon-enhanced tissue-specific expression. The region from -0.11 to -0.66 kb is also sufficient to prevent integration site-specific "position effects," because in its absence HLA-B7 expression is frequently detected at significant levels at inappropriate sites. Conserved sequence elements homologous to the H-2 class I regulatory element, or enhancer A, and the interferon response sequence are located between about -151 and -228 bp of the B7 gene. Our results also indicate the existence of sequences downstream of -0.11 kb which can influence the pattern of tissue-specific expression of the HLA-B7 gene and the ability of this gene to respond to gamma interferon.

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