Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors

Here we describe the cloning and initial characterization of a previously unidentified CRF-related neuropeptide, urocortin II (Ucn II). Searches of the public human genome database identified a region with significant sequence homology to the CRF neuropeptide family. By using homologous primers deduced from the human sequence, a mouse cDNA was isolated from whole brain poly(A)+ RNA that encodes a predicted 38-aa peptide, structurally related to the other known mammalian family members, CRF and Ucn. Ucn II binds selectively to the type 2 CRF receptor (CRF-R2), with no appreciable activity on CRF-R1. Transcripts encoding Ucn II are expressed in discrete regions of the rodent central nervous system, including stress-related cell groups in the hypothalamus (paraventricular and arcuate nuclei) and brainstem (locus coeruleus). Central administration of 1–10 μg of peptide elicits activational responses (Fos induction) preferentially within a core circuitry subserving autonomic and neuroendocrine regulation, but whose overall pattern does not broadly mimic the CRF-R2 distribution. Behaviorally, central Ucn II attenuates nighttime feeding, with a time course distinct from that seen in response to CRF. In contrast to CRF, however, central Ucn II failed to increase gross motor activity. These findings identify Ucn II as a new member of the CRF family of neuropeptides, which is expressed centrally and binds selectively to CRF-R2. Initial functional studies are consistent with Ucn II involvement in central autonomic and appetitive control, but not in generalized behavioral activation.

Dual HLA class I and class II restricted recognition of alloreactive T lymphocytes mediated by a single T cell receptor complex

The alloreactive human T cell clone MBM15 was found to exhibit dual specificity recognizing both an antigen in the context of the HLA class I A2 molecule and an antigen in the context of the HLA class II DR1. We demonstrated that the dual reactivity that was mediated via a single clonal T cell population depended on specific peptide binding. For complete recognition of the HLA-A2-restricted specificity the interaction of CD8 with HLA class I is essential. Interestingly, interaction of the CD8 molecule with HLA class I contributed to the HLA-DR1-restricted specificity. T cell clone MBM15 expressed two in-frame T cell receptor (TCR) Vα transcripts (Vα1 and Vα2) and one TCR Vβ transcript (Vβ13). To elucidate whether two TCR complexes were responsible for the dual recognition or one complex, cytotoxic T cells were transduced with retroviral vectors encoding the different TCR chains. Only T cells transduced with the TCR Vα1Vβ13 combination specifically recognized both the HLA-A2+ and HLA-DR1+ target cells, whereas the Vα2Vβ13 combination did not result in a TCR on the cell surface. Thus a single TCRαβ complex can have dual specificity, recognizing both a peptide in the context of HLA class I as well as a peptide in the context of HLA class II. Transactivation of T cells by an unrelated antigen in the context of HLA class II may evoke an HLA class I-specific T cell response. We propose that this finding may have major implications for immunotherapeutic interventions and insight into the development of autoimmune diseases.

A common major histocompatibility complex class II allele HLA-DQB1* 0301 is present in clinical variants of pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease seen primarily in elderly persons. It is characterized clinically by the development of tense bullae and by the presence of an antibasement membrane antibody. In BP, the antigens involved in the autoimmunity are epidermal basement membrane peptides BPAg1 and BPAg2. We have compared high resolution typing of major histocompatibility complex class II loci (HLA-DRB1, DQB1) in 21 patients with BP, 17 with ocular cicatricial pemphigoid (OCP), and 22 with oral pemphigoid (OP) to a panel of 218 haplotypes of normal individuals. We found that the three diseases (BP, OCP, and OP) have significant association with DQB1*0301 (P = 0.005, P < 0.0001, and P = 0.001, respectively). The frequencies of alleles DQB1*0302, 0303, and 06, which share a specific amino acid sequence from position 71 to 77 (Thr-Arg-Ala-Glu-Leu-Val-Thr) were also increased (P = 0.01). We suggest that an identical major histocompatibility complex class II allele (DQB1*0301) is a common marker for enhanced susceptibility and that the same amino acid residues in positions 71-77 (DQB1*0301, -0302, -0305, -0602, -0603 alleles) are found in patients with BP, OCP and OP. Our findings propose that the autoimmune response in the three different clinical variants of pemphigoid, involves the recognition by T cells of a class II region of DQB1, bound to a peptide from the basement membrane of conjunctiva, oral mucosa, and skin.

[Admittatur of Samuel Abbot Kneeland (Harvard AB 1797)], 1793 August 15

Published copy of the 1790 College Laws, with the admittatur of undergraduate Samuel Abbot Kneeland signed by President Joseph Willard on August 15, 1793.

[Admittatur of Henry Gardner (Harvard AB 1798)], 1794 August 13

Published copy of the 1790 College Laws, in a modern hardcover binding, with the admittatur of undergraduate Henry Gardner signed by President Joseph Willard on August 13, 1794.

[Admittatur of Samuel Weed (Harvard AB 1800)], 1796 August 17

Published copy of the 1790 College Laws, bound in modern board binding, with the admittatur of undergraduate Samuel Weed signed by President Joseph Willard on August 17, 1796.

[Admittatur of Timothy Fuller (Harvard AB 1801)], 1797 August 18

Published copy of the 1790 College Laws with the admittatur of undergraduate Timothy Fuller signed by President Joseph Willard on August 18, 1797.

[Admittatur of Benjamin Merrill (Harvard AB 1804)], 1800 August 12

Published copy of the 1790 College Laws with the admittatur of undergraduate Benjamin Merrill signed by President Joseph Willard on August 12, 1800. Four pages of amendments of and additions to the Harvard Laws "enacted since the Summer of 1798, and are now in force Dec. 1, 1800" are tipped in at the beginning of the volume.

[Admittatur of John Law (Harvard AB 1804)], 1802 March 1

Published copy of the 1798 College Laws with the admittatur of undergraduate John Law signed by President Joseph Willard on March 1, 1802.

[Admittatur of Jacob Cushing Merrill], 1803 September 28

Published copy of the 1798 College Laws with the admittatur of undergraduate Jacob Cushing Merrill signed by President Joseph Willard on September 28, 1803.

[Admittatur of Nathanael Appleton Haven], 1803 September 29

Published copy of the 1798 College Laws with the admittatur of undergraduate Nathanael Appleton Haven signed by President Joseph Willard on September 29, 1803.

[Admittatur of Thomas Lindall Winthrop], 1803 September 29

Published copy of the 1798 College Laws with the admittatur of undergraduate Thomas Lindall Winthrop signed by President Joseph Willard on September 29, 1803.

[Admittatur of Andrew O. Waterhouse], 1806 September 24

Published copy of the 1807 College Laws with the admittatur of undergraduate Andrew O. Waterhouse signed by President Samuel Webber on September 24, 1806.

[Admittatur of Simeon Putnam], 1807 September 23

Published copy of the 1807 College Laws with the admittatur of undergraduate Simeon Putnam signed by President Samuel Webber on September 23, 1807.

[Admittatur of John Walsh], 1811 February 25

Published copy of the 1807 College Laws with the admittatur of undergraduate John Walsh signed by President John Kirkland on February 25, 1811.